Brian G. Blackburn, MD

• Clinical Associate Professor
• Internal Medicine/Infectious Diseases and Geographic Medicine Stanford University School of Medicine

Higher doses of naicin can cause hepatotoxicity and gastrointestinal side effects cholesterol in cooked eggs generic caduet 5mg otc. Idiopathic nightmares and dream disturbances associated with sleep-wake transitions cholesterol yolk buy 5mg caduet with amex. Treatment Complications: Psychotherapy aimed at resolving conflict has been the treatment of choice historically cholesterol medication names uk caduet 5mg on line, but little evidence is available supporting its use is cholesterol in shrimp good or bad for you order caduet us. Other treatments include lucid dreaming average cholesterol japan caduet 5mg lowest price, eye movement desensitization and reprocessing cholesterol of 260 5mg caduet with visa, and hypnosis. Other medications, though not as well studied, are available for use as potential therapy including clonidine, trazodone, and risperidone. Nitrous Oxide and the Inhalation Anesthetics Epidemiology and Demographics: Common users are Disorder Description: the inhalation agents are most young males/adolescents. They are excellent hypnotics resulting in analgesia and skeletal muscle relaxation. Nitrous oxide, commonly known as "laughing gas," is an inorganic inhalation agent that is colorless, odorless to sweet-smelling, and non-irritating to the tissues. The brain as a dream state generator: an activation-synthesis hypothesis of the dream process. Imagery rehearsal therapy for chronic nightmares in sexual assault survivors with posttraumatic stress disorder: a randomized controlled trial. Spinal cord Anterior horn cells Conus medullaris Cauda equina Specific spinal roots 421 Section 1 Diagnostics Localization site Plexus Mononeuropathy or mononeuropathy multiplex Comment Analgesic effect (acute) Paresthesias (acute) Peripheral neuropathy Peripheral neuropathy (chronic) Polyneuropathy (chronic) Muscle Syndromes with combined spinal cord and peripheral nerve lesions Hypotonia (acute) Subacute combined degeneration neuropathy secondary to nitrous oxide ("laughing gas") abuse that had affected vitamin B12 activation commonly occurs in the lungs by inhalation of dust containing the bacteria. Immunocompromised individuals are at risk, but about a third of reported cases are in otherwise healthy individuals. Disorder Description: Nocardia is an aerobic, grampositive actinomycetes-like bacterium that uncommonly affects humans. Inactivation of vitamin B12 by nitric oxide enzymes causes vitamin B12 dysfunction, resulting in peripheral neuropathy. Localization site Cerebral hemispheres Comment the hallmark is development of a brain abscess. In one review of 131 cases of nocardial brain abscess, focal deficits occurred in 42%, nonfocal findings in 27%, and seizures in 30%. Mortality is three times higher than that of other bacterial brain abscesses (30% vs 10%) Sagittal sinus thrombosis, hemorrhagic and ischemic infarcts have been described Mental status changes are as per location of brain abscess and features of raised intracranial pressure. Brainstem involvement and seizures can lead to declining consciousness Brainstem abscesses have been described Endophthalmitis and subretinal abscess have been reported. Brainstem involvement may lead to other cranial nerve involvement Spinal cord abscess and cord compression have been described. Nocardia species are typically found in standing water, decaying plants, and soil. However, nocardiosis most Spinal cord Unclear localization Secondary Complications: Long-term sequelae of lobar abscess includes functional deficit subserved by the focal region of the brain. Given that subspecies of Nocardia exhibit differential susceptibilities, formal antimicrobial susceptibility testing is always necessary to ensure optimal antibiotic treatment. Treatment complications include morbidity of surgery and hypersensitivity to medication. Nocardiosis of the central nervous system: experience from a general hospital and review of 84 cases from the literature. Symptoms Localization site Cranial nerves Comment Painless visual loss secondary to ischemia to optic nerve, usually first noticed upon awakening. The cup:disc ratio is usually small on funduscopic exam, and the disc is pale and edematous Secondary Complications: Bilateral visual loss (20% of Treatment Complications: Treatment of non-arteritic cases). Comorbid vascular risk factors (hypertension, diabetes mellitus, and hyperlipidemia) are associated with this disease. Disorder Description: the central retinal artery and the short and long posterior ciliary arteries are the major branches off the ophthalmic artery and are the predominant blood supply to the optic nerve. Levodopa may improve vision loss in recentonset, nonarteritic anterior ischemic optic neuropathy. Hypothesis: a venous etiology for nonarteritic anterior ischemic optic neuropathy. May manifest as change in behavior or altered mental state, with bizarre behaviors, language disturbance, perceptual changes, or lethargy and obtundation. May be accompanied by subtle motor manifestations such as lip and lid twitching or gaze abnormalities. Treatments generally include intravenous benzodiazepines as first line, phenytoin and valproate as second line therapies, and levetiracetam, lacosamide, topiramate, barbituates, or other sedative agents such as propofol or midazolam as additional options. Treatment Complications: Benzodiazepines are sedating and can cause respiratory depression. Phenytoin infusion may induce cardiovascular instability, ataxia, dizziness, frozen glove syndrome, and rash. Valproate side effects include weight gain, hyperactivity, transaminitis, thrombocytopenia, and pancreatitis. New understanding of nonconvulsive status epilepticus in adults: treatments and challenges. They usually occur during the first third of sleep with absent or inappropriate responsiveness when others intervene during the episode. Symptoms Localization site Cerebral hemispheres Comment Absence, myoclonic absence, or focal status epilepticus. Associated with palpebral myoclonia, limb and oroalimentary automatisms, dystonic posturing, twitching of the face or limbs, rhythmic nystagmus or gaze deviation Alterations in awareness. The resulting sleep disturbances can result in severe daytime sleepiness and somnolence and the effects of sleep deprivation are seen as well. O In addition, pulmonary hypertension with cor pulmonale, polycythemia vera, and neurocognitive dysfunction may be seen. Treatment Complications: Treatment includes weight loss, continuous positive airway pressure, and the use of noninvasive ventilation in the form of bilevel positive airway pressure. Other modes of noninvasive ventilation such as average volume assured pressure support also have utility in management of this condition. Pharmacotherapy using medroxyprogesterone can lead to increased risk of venous thromboembolism. Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. Hypersomnolence, and mood and cognitive disturbances are common among these patients. Other consequences of chronic hypercapnia and hypoxemia include risk of respiratory failure and need for hospitalization particularly in association with simultaneous respiratory illness. Adult females are more frequently affected than adult males, but male children are more frequently affected than female children. Recurrent and persistent thoughts, urges, or images that are experienced at some time during the disturbance as intrusive and unwanted, and that in most individuals cause marked anxiety or distress. The individual attempts to ignore or suppress such thoughts, urges, or images, or to neutralize them with some other thought or action. The behaviors or mental acts are aimed at preventing or reducing anxiety or distress, or preventing some dreaded event or situation; however, these behaviors or mental acts are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive. The obsessive-compulsive symptoms are not attributable to the physiologic effects of a substance (drug of abuse, medication) or another medical condition. The disturbance is not better explained by the symptoms of another mental disorder. Differential Diagnosis: Differential diagnosis should include anxiety disorders, other obsessivecompulsive and related disorders, eating disorders, tics and stereotyped movements, psychotic disorders, and other compulsive-like behaviors. In other obsessive-compulsive and related disorders, there may also be obsessions and/or compulsions. For example, in trichotillomania, the compulsive behavior is limited to hair pulling in the absence of obsessions. In hoarding disorder, symptoms focus exclusively on difficulty parting with objects. In eating disorders, obsessions and compulsions are limited to concerns about weight and food. In tics and stereotyped movements, the occurrences are typically less complex than compulsions and are not aimed at neutralizing obsessions. Whereas compulsions are usually preceded by obsessions, tics are generally preceded by premonitory sensory urges. In the psychotic disorder delusional disorder, there are no obsessions followed by compulsions, and in schizophrenia and related disorders, there are hallucinations or problems in formal thought processes. In obsessive-compulsive personality disorder, there are not necessarily intrusive thoughts, images, or urges, or compulsions in response to such obsessions. Instead, obsessive-compulsive personality disorder is characterized by an enduring and pervasive maladaptive pattern of excessive perfectionism and rigid control. Excessive time may be spent obsessing and performing compulsions, and may result in tardiness to obligations or missed deadlines. Obsessions about harm may make interpersonal relationships difficult as they may be perceived as dangerous. Obsessions about symmetry may make completion of school or work projects difficult or impossible. Symptoms of overdose include agitation, tremors, ataxia, arrhythmias, delirium, hypoventilation (secondary to central nervous system depression), myoclonus, hyperreflexia, seizures, and coma. Atypical antipsychotic side effects include metabolic syndrome, weight gain, hyperlipidemia, and hyperglycemia. Local cerebral glucose metabolic rates in obsessivecompulsive disorder: a comparison with rates in unipolar depression and in normal controls. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Lifetime prevalence, age of risk, and 427 Section 1 Diagnostics genetic relationships of comorbid psychiatric disorders in Tourette syndrome. Symptoms Localization site Mental status and psychiatric aspects/ complications Comment Mood disturbances, including depression, anxiety. Disorder Description: Obstructive sleep apnea is characterized by repetitive obstructions of the upper airway, each episode lasting for a minimum of 10 seconds. Complete obstructions (apneas) or partial obstructions (hypopneas) can result in sleep fragmentation from frequent arousals, intermittent hypoxia, and heart rate variability. Women may also report symptoms of insomnia, mood disturbances, and poor sleep quality. Diagnosis is made based on diagnostic polysomnography or home sleep apnea testing. Treatment Complications: Standard therapy for obstructive sleep apnea includes continuous positive airway pressure therapy, which delivers positive airway pressure through a nasal or full face mask to prevent upper airway collapse. Other treatment options include mandibular advancement oral appliance, maxillofacial surgery, and uvulopalatalpharyngoplasty. Maxillomandibular advancement therapy carries the risks of occlusal changes and temporomandibular joint discomfort. In benign occipital epilepsies of childhood, age of onset is between 3 and 15 years. This can include visual auras and/or elementary visual hallucinations, ictal blindness, contralateral eye and head deviation, eye movement sensations, blinking, and eyelid flutter. Studies have reported that occipital spike and wave discharges are detected in 17% of patients interictally and 30% ictally. May occur secondary to cortical malformations, such as dysgenesis or occipital periventricular heterotopias; or due to toxic-metabolic conditions such as reversible posterior leukoencephalopathy. Significant improvement in seizure control with resection of area has been reported in up to 80% of cases. In early childhood occipital epilepsy, seizures spontaneously remit by the end of adolescence and rarely recur. Treatment Complications: Postoperative visual field deficits can occur if symptomatic lesions are removed surgically. Carbamazepine is recommended for the idiopathic childhood epilepsies, but may be associated with hyponatremia, leukopenia, transaminitis, and issues such as bone loss and decreased libido in adults. Intractable occipital lobe epilepsy: clinical characteristics, surgical treatment, and a systematic review of the literature. Occipital Neuralgia Epidemiology and Demographics: There are no epidemiological studies that document the incidence or prevalence of occipital neuralgia. Disorder Description: the hallmark presentation of occipital neuralgia involves paroxysmal lancinating pain that is described as stabbing, shooting, electric, or shock-like. Symptoms are associated with allodynia of the scalp in the distribution of the nerve (C2, C3 branches). However, antiepileptic drugs have been used with success in reducing frequency and severity of attacks. Occipital nerve block is also a consideration but small case reports show that the pain returns, with average length of relief of 31 days. Greater occipital nerve injection in primary headache syndromes: prolonged effects from a single injection. Additional extrapyramidal side effects that can be seen with neuroleptic drugs include Parkinsonism (bradykinesia, cogwheel rigidity, pill-rolling tremor, and bradykinesia) and akathisia (an uncomfortable, subjective sense of restlessness that may manifest as fidgeting).

If we assume that M1 is the entire known effect of the active control relative to placebo [11] cholesterol medication atorvastatin side effects cheap caduet line, and this has been determined based on historical data derived from comparison of active control versus placebo or no treatment definition of cholesterol in the body buy caduet 5mg with visa, then M1 should be the smallest reliable effect size demonstrable free cholesterol test orange county discount caduet line. The determination of the smallest effect size for C is critical cholesterol levels explained discount 5mg caduet overnight delivery, because if the new treatment is less effective than the active control and the magnitude of this difference is greater than the smallest reliable effect size of the active control cholesterol your body makes order 5mg caduet, the new treatment may have no effect at all cholesterol levels recommended uk cheap caduet 5 mg overnight delivery. Different approaches have been proposed for establishing it based on statistical reasoning; however, all of them require using the results of one or more historical placebo-controlled studies of the active treatment to determine the effect of the active control versus placebo. It can be constructed from meta-analysis using a random/fixed effects model approach. This margin incorporating clinical 140 Textbook of Clinical Trials in Oncology judgment also is sometimes referred to as margin 2 (M2) [11]. Incorporating clinical judgment into M is subjective and little has been published on a recommended procedure. The clinically relevant margin of indifference often is described as determining the largest loss of effectiveness of the new treatment that would be considered clinically insignificant. Obviously, the selected value may vary substantially among individuals, and may likely vary within an individual on a case-by-case basis. Furthermore, the severity of the disease state being treated strongly determines the magnitude of M. To ensure that the new treatment has some effect, the selected M cannot be greater than the smallest reliable effects size. The most common procedure for selecting M is for it to be half of M1 to maintain at least half of the clinical effect of the active control. An alternative, less-conservative approach is to be half of the point estimate of the effect of active control over placebo, and then select the smaller of this value and M1 to ensure that M is M1. However, in reality, there is no "one-size-fits-all" approach to selecting M because of inherent subjectivity in using clinical judgment. The smaller the margin, the lower the upper bound of the 95% twosided confidence interval for C - T must be, and the larger the sample size needed to establish non-inferiority. The margin of interest, however, as noted above, is usually smaller than M1 (to show that an adequate portion of the clinical benefit of the control is preserved). One strategy is to use a fixed-margin approach (preserve a fraction of the effect). On the other hand, if the noninferiority margin is too large, it may lead to the approval of some treatments which have only slight or no benefit to patients. This is not measured in the trial but must be known or estimated from previous studies of C, generally versus placebo (P). The effect represented by M should be no larger than the entire effect of the drug. If C - T were larger than M, then a non-inferiority finding could represent a loss of all of the effect versus the control. If the desired retention is very high, for example, 90%, as noted above, studies become very large or, as a practical matter, only drugs that are actually superior will be successful. By demonstrating that the new treatment is no less effective than the control within the margin, the efficacy of the new treatment would have been established over placebo had the placebo arm existed in the trial. The nominal significance level for this one-sided test is generally set at half of the conventional significance level for a two-sided test for the difference in treatment effect between comparison groups (usually one-sided = 0. In cancer clinical trials, this outcome could be 142 Textbook of Clinical Trials in Oncology the objective response status. Hazard ratio between groups is usually used to measure the difference and are compared using the log-rank test. The synthetic estimate or test is used to assess the efficacy of the new treatment versus a putative placebo and to estimate the fraction of the control effect that may have been preserved by the new treatment had the placebo been present in the active-controlled trial. The effect of the active control is obtained from historical placebo-controlled trials that are independent of the active-controlled trial to be undertaken. Several authors, including Holmgren [23], Hasselblad and Kong [24], and Fisher [25], had proposed the method. The estimates of the effect could the risk difference; logarithm of relative risk for a binary outcome, or ^ ^ logarithm of hazard ratio for a time-to-event outcome. Insufficiently sized trials would lead to statistically Non-Inferiority Trial 145 inclusive results, failing to give a conclusive decision. Sample size derivation should be based on the statistical procedure used to draw the conclusion of the study, reflecting the primary study objective. Different types of study and primary endpoints lead to different sample size estimation methods. Let 2 be the common variance population variance of the treatment effect summary statistic for each study treatment arm, Z1- be the 100(1 -) percentile of a standard normal distribution. Let r be the ratio of patients randomized between the experimental and the control arm. For a 1-to-1 ratio of randomization, the sample size is estimated as n = 4 * (Z1- + Z1-)2 2 /(a - M)2. Many authors have investigated the method for determining the sample size, the methods and formulas devised by Freedman [28], Schoenfeld [29], and Schoenfeld and Richter [30] which have particularly simple assumptions and are arguably the tools most widely used. It should be pointed out that, for the time-to-event endpoint, the number of events is the key to ensure the power of the study. Due to the changes in patients care, the projected event rate at the design stage might not be very accurate; the duration of the trial might vary to get the required number of events. The use of a placebo control will not preclude potential study subjects from giving informed consent to participate the study; 3. An active control is available that will provide additional information about the benefit and/or risk of the experimental medication compared with other available therapy. It is generally acceptable for fixed-sequence hierarchical tests without adjusting for the multiple tests [35]. However, multiple tests in the further secondary analyses should be adjusted among themselves to control the overall type I error in those secondary analyses. The group sequential designs allow interim analyses based on the cumulative data to specified time points with a decision rule to either continue or stop the study [37]. Ethical considerations have been used for the rationale for interim analyses for efficacy, futility, or harm. If the experimental therapy is highly effective, it is imperative to allow patients access to such treatment; on the other hand, if the experimental therapy is lacking efficacy or is harmful, early evidence could stop the study early, restricting patients from continuing the futile/harmful treatment. However, if experimental therapy is worse than the control, stopping the study early is justified. For the historical comparison to have operational validity in the current trial, the critical assumption of constancy must be met. Incomplete or inaccurate ascertainment of outcomes because of loss to follow-up, treatment crossover or nonadherence, or outcomes that are difficult to measure or are subjective may cause the treatments being compared to falsely appear similar. The quality of the trial(s) conducted with the selected active control compared with the placebo is also important. A high-quality, well-described trial demonstrating the effectiveness of the active control ensures a high degree of confidence that the effect is reproducible. As the randomization is essential for achieving the comparability and the basis for statistical inference, this approach is favored as it preserves randomization and, in the case of departures from randomized treatment, makes treatment groups appear more similar; therefore, producing a conservative estimate of treatment effect. However, in the non-inferiority setting, because the null and alternative hypotheses are reversed, a dilution of the treatment effect actually favors the alternative hypothesis, making it more likely that true inferiority is masked. Because non-completers are not included, it can distort the reported effectiveness of a treatment. If, for example, a significant percentage of participants dropped out of the experimental treatment because they felt the treatment received was ineffective, the per-protocol analysis would not adequately capture that. While selection bias is thought to be minimized in trials with blinding, and modified definitions of these populations that adjust for observed confounders can be used, selection bias can never be completely discounted from any analyses that makes post-randomization exclusions or manipulations. Regardless of the approach used, the reported findings should specify and fully describe the type analysis population. Similar results from both analyses are expected, and contraction findings may revere issues in trial conduction. Under conventional hypothesis testing in a comparative study of two interventions, the goal is to reject the null in favor of a difference between the two interventions. Rather, failure to reject the null means that there is not sufficient evidence to accept the alternative hypothesis. We recommend that both confidence interval and p-values be provided to allow the audience to interpret the extent of the findings. An important consideration in choosing a missing data approach is the missing data mechanism, and different approaches have different assumptions about the mechanism. The data missing mechanism describes the possible relationship between the propensity of data to be missing and values of the data, both missing and observed. There is no systematic trend that makes some data more likely to be missing than others. This is a case where the people with the lower education are missing on education or the sickest people are most likely to drop out of the study. You have to include some model for why the data are missing and what the likely values are. Multiple imputation and maximum likelihood [43,44] assume the data are at least missing at random. It should be pointed out that in most datasets, more than one variable can have missing data, and they may not all have the same mechanism. The best approach of dealing with missing data is to prevent missing data, so high quality of trial conduction is key for reliable results. Analysis in the presence of missing data are typically with two objectives: unbiased estimation of treatment effect and making valid inference under the null hypothesis. For handling ignorable missing, multiple imputation under the null hypothesis is recommended [44]. For example, continuous endpoint: impute reasonable expected value (m) for the active control and (m-M) for the new intervention. For binary data: impute expected proportion (p) for active control and (p-M) for new intervention. However, to assess the robustness of the outcome, certain biased imputation can be used. For example, for binary endpoint: impute success for the active control and failure for new intervention. Was the efficacy displayed by the control group similar to that shown in trials versus placebo (constancy) Detailed information on the study can be found in the publication of the trial by Crump et al. To use a one-sided 5% level test, with 80% power under the alternative hypothesis that the response rates are equal, we needed to accrue a total of 630 patients. The primary per-protocol analyses, the response rates after two cycles of treatment were 46. For the intention-to-treat analysis, the response rate after two cycles of treatment was 45. In order to rule out the difference with 80% power using a one-sided 5% level test assuming that we are using a point of indifference [49] at a hazard ratio of 1. Declaration of Helsinki: Ethical principles for medical research involving human subjects. Non-inferiority trials: Design concepts and issues- the encounters of academic consultants in statistics. Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration: Non-Inferiority Clinical Trials to Establish Effectiveness, Guidance for Industry. Equivalence and noninferiority trials: Are they viable alternatives for registration of new drugs Showing a treatment is good because it is not bad: When does non-inferiority imply effectiveness A regulatory perspective on choice of margin and statistical inference issue in non-inferiority trials. Establishing equivalence by showing that a specified percentage of the effect of the active control over placebo is maintained. Tables of the number of patients required in clinical trials using the logrank test. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Assessing the therapeutic equivalence of two treatments in comparison with a placebo group. Establishing non-inferiority of a new treatment in a three-arm trial: Apply a step-down hierarchical model in a papulopustular acne study and an oral prophylactic antibiotics study. A comparison of intent-to-treat and per-protocol results in antibiotic noninferiority trials. Power function arguments in support of an alternative approach for analyzing management trials. As of a few years ago there were more than 1,500 new pharmaceutical treatments for oncology in the pipeline [1]. If one also considers potentially testing of multiple doses of a particular 155 156 Textbook of Clinical Trials in Oncology treatment, multiple combinations of distinct treatments, and multiple schedules of treatments, it is easy to see that there are a huge number of potential treatment arms to test in clinical trials. Conducting randomized controlled trials of each available treatment arm may lead to too many trials competing for the limited number of patients that can be enrolled. If traditional two-arm randomized controlled trials are to be used, then either the number of treatments to be tested must be reduced, or trials will risk being underpowered. An alternative approach is to test several experimental treatments within a single trial. There are several main advantages to a multi-arm trial, compared to several separate trials, as described in Parmar et al.

The prevalence increases with age and is estimated to be 2/1000 in females older than 60 years of age cholesterol definition wikipedia order 5mg caduet mastercard. Secondary hyperparathyroidism occurs in patients with dialysis-dependent chronic kidney disease and may progress to tertiary hyperparathyroidism cholesterol test price in india purchase generic caduet canada. Children in poor and developing countries may develop nutritional rickets cholesterol ratio of 2.6 buy caduet 5 mg on-line, a form of secondary hyperparathyroidism cholesterol medication makes me sick generic 5 mg caduet otc. Risk factors include genetic predisposition to hyperparathyroidism and childhood exposure to external neck irradiation definition de cholesterol hdl caduet 5 mg low cost. Disorder Description: Solitary parathyroid adenoma is the most common cause of primary hyperparathyroidism (85%) and results from the oversecretion of parathyroid hormone cholesterol lowering diet plan mayo clinic purchase generic caduet pills. Other causes include multiple parathyroid adenoma, parathyroid hyperplasia, and ectopic parathyroid glands. Secondary hyperparathyroidism is seen in chronic kidney disease and vitamin D deficiency and results from the compensatory oversecretion of parathyroid hormone secondary to abnormalities in calcium metabolism. Other less common causes include pseudohypoparathyroidism, metastatic prostate cancer, cholestatic liver or biliary disease, malabsorption, and medications (lithium, anticonvulsants, ketoconazole, rifampin, leucovorin). Cerebellum Base of skull Spinal cord Anterior horn cells Mononeuropathy or mononeuropathy multiplex Peripheral neuropathy Muscle Syndromes with combined upper and lower motor neuron deficits Paresthesia Proximal weakness, muscle pain, and stiffness May mimic amyotrophic lateral sclerosis Secondary Complications: Hypercalcemia and nephro- lithiasis are commonly seen. Chrondrocalcinosis, fractures, osteoporosis (from progressive bone loss), and episodes of acute gout can occur in patients with primary hyperparathyroidism. Osteitis fibrosa cystica (subperiosteal bone resorption in the distal phalanges and skull) can be seen in patients with secondary hyperparathyroidism, secondary to renal failure. Acute or subacute monoarticular inflammatory arthritis may develop from calcium pyrophosphate dihydrate crystal arthropathy. Some studies suggest that these patients may be insulin resistant and at greater risk for cardiovascular events. Cinacalcet is used to lower serum calcium levels but it does not normalize parathyroid hormones or prevent future bone loss. Symptoms Localization site Comment Cerebral hemispheres Headache due to mass effect Mental status and psychiatric aspects/ complications Anxiety and depression may occur independent of comorbid psychiatric illness or treatment with antipsychotics Mass effect causing visual and olfactory hallucinations due to perceptual disturbances as well as episodes of "losing time," and apathy have been reported Visual complaints due to mass effect Hypopituitarism in men due to delayed diagnosis Bibliography Brown R, Fischman A, Showalter C. Primary hyperparathyroidism, hypercalcemia, paranoid deluisons, homicide and attempted murder. Sex hormone, pituitary, parathyroid, and adrenal disorders and the nervous system. Cranial nerves Pituitary gland Treatment Complications: Dopamine agonist treatment for prolactinomas may induce or exacerbate psychotic symptoms. Etiologies and clinical manifestations of hyperprolactinemia in a medical center in Southern Taiwan. Department of Internal Medicine, Department of Pharmacy National Cheng Kung University Hospital, Tainan, Taiwan. Other less common causes of hyperprolactinemia include decreased dopamine inhibition of prolaction secretion, hypothalamic or pituitary disorders, and drug induced (mainly antipsychotics). Disorder Description: Prolactin is a hormone, mainly secreted by the lactotroph cells of the anterior pituitary gland. Hyperprolactinemia leads to amenorrhea, infertility, and galactorrhea in women and decreased libido and impotence in men. Long-standing uncontrolled hypertension induces lipohyalinosis in small vessels that leads to end-organ ischemic damage. Hypertension can also increase risk of bleeding by persistently loading pressure to weak points of small vessel walls. Hypertensive Crisis Epidemiology and Demographics: One percent to 5% of patients with hypertension will develop a hypertensive crisis in their lifetime. It is commonly caused by sudden escalation of chronic essential hypertension, drug interaction, or withdrawal from antihypertensive drugs. Disorder Description: "Hypertensive crisis" contains two concepts: hypertensive urgency and emergency. If acute symptomatic end-organ ischemic damage occurs with hypertensive urgency, it is called hypertensive emergency. Symptoms Localization site Comment Cerebral hemispheres Chronic hypertension is classical risk factor for stroke and transient ischemic attack, especially lacunar strokes. Chronic hypertension also increases risk of intraparenchymal hemorrhage, usually in deep brain areas. Subarachnoid hemorrhage occurs secondary to aneurysmal rupture Large intraparenchymal or subarachnoid hemorrhage commonly induces mental status deterioration. If patients are awake, they usually complain of sudden onset severe headache Chronic hypertension increases risk of brainstem lacunar infarct and hemorrhage Risk of cerebellar lacunar infarct and hemorrhage is also increased. In case of large cerebellar hemorrhage, expansion to 4th ventricle is common and risk of cerebral aqueduct occlusion is high Cranial symptoms usually present as a part of brainstem infarction or hemorrhage Symptoms Localization site Cerebral hemispheres Comment Both ischemic and hemorrhagic stroke can be caused by hypertensive crisis. These result in acute onset of focal cortical symptoms, such as hemiparesis, aphasia, or hemiparesthesia. Acute onset of headache and confusion or lethargy are common with hemorrhages If diffuse, higher cortical symptoms are seen in hypertensive crisis, which is called hypertensive encephalopathy. Various cortical symptoms can be seen, including headache, confusion, restlessness, altered consciousness, and seizures. Retinal hemorrhages can be induced by hypertensive crisis as well Mental status and psychiatric aspects/ complications Brainstem Cerebellum Mental status and psychiatric aspects/ complications Cranial nerves Secondary Complications: Cardiovascular complications of hypertension. Treatment Complications: Supratherapeutic antihypertensive medication dosing can cause decreased cerebral blood flow, which leads to depressed mentation. Sudden onset of congestive heart failure may occur because of the extremely high afterload. Treatment Complications: Intravenous antihypertensive agents are the choice of treatment for hypertensive emergency. It is important not to drop the mean arterial pressure by more than 25% during the first 24 hours to avoid hypoperfusion brain injury such as watershed infarct. This 25% rule may apply for several days so that careful clinical follow-up is essential on further lowering of blood pressure. Localization site Peripheral neuropathy Comment Axonal sensory polyneuropathy and rarely demyelinating polyneuropathy Basedow paraplegia acutely in the hyperthyroid state6 characterized by weakness and areflexia Carpel tunnel syndrome in thyrotoxicosis High-frequency low-amplitude tremor and hyperreflexia with thyrotoxicosis due to stimulation of the beta adrenergic system. Proximal muscle weakness with normal creatine kinase levels Muscle Bibliography Biller J. Secondary Complications: Stroke as a result of thyrotoxic Hyperthyroidism Epidemiology and Demographics: More common in women than men (5:1 ratio). Cerebral venous thrombosis as a result of an induced hypercoagulable state due to hyperthyroidism may occur. Treatment Complications: Antithyroid medications propylthiouracil and methimazole may cause arthralgia or myalgia. Adverse effects of these therapies include hypothyroidism that often warrants thyroid hormone supplementation. Symptoms Localization site Cerebral hemispheres Comment Encephalopathy and seizure activity with thyroid storm. These mutations result in a thickened (hypertrophied) yet nondilated left ventricle and irregularities of the mitral valve, which in many cases leads to an outflow tract obstruction. An alternative procedure is alcohol septal ablation, which carries similar risks of morbidity and mortality. An implantable defibrillator may be used for patients with high risk of sudden death; in addition common medications include beta blockers and calcium channel blockers. Symptoms Localization site Cerebral hemispheres Comment Cerebral hypoperfusion resulting in symptoms of presyncope and/or syncope as a result of outflow tract obstruction if present. In addition, secondary arrhythmias may also provoke similar hypoperfusion with presyncope/ syncope and potentially sudden death Dizziness, lightheadedness, and confusion along with impairment of consciousness plus syncope and presyncope Same as above Same as above Hyperventilation Syndrome Epidemiology and Demographics: In those with an anxiety disorder, studies show a wide range of prevalence from 25 to 83%. It occurs intermittently, typically lasts minutes to hours and resolves on its own. It is often accompanied by symptoms of dyspnea, dizziness, palpitations, chest tightness, paresthesias, and/or carpopedal spasm. It is commonly associated with panic disorder, but which process is primary or secondary is unclear. When associated with distressing psychologic processes, symptoms include the feeling that one is not getting enough air, shallow and irregular breathing patterns, and frequent sighing. Treatment Complications: A treatment used for patients with severe symptoms is surgical myectomy whose risks include infection, arrhythmias, myocardial 287 Section 1 Diagnostics associated with hyperventilation that is associated with psychiatric disorders. Many disorders can present with hyperventilation, but a diagnosis of hyperventilation syndrome implies there is no known underlying cardiac, pulmonary, metabolic, or other medical etiology. Symptoms Localization site Cerebral hemispheres Comment Differential diagnosis: central hyperventilation syndrome (pontine lesion), post-ictal hyperventilation Anxiety, fear, and panic macroglobulinemia (85%) and less frequently from multiple myeloma or disorders with elevated blood counts such as leukemia or polycythemia. White blood cell counts are generally over 100,000/L in leukemias, while in polycythemia, the hemoglobin level is usually greater than 18 g/dL. Disorder Description: Red blood cells typically determine blood viscosity in healthy individuals. In hyperviscosity syndrome with paraproteinemia, excess protein forms aggregates increasing resistance to flow. In disorders with elevated blood counts, there is leukostasis resulting in sluggish flow. Mental status and psychiatric aspects/complications Vestibular system (and nonspecific dizziness) Peripheral neuropathy Symptoms Localization site Cerebral hemispheres Comment Diffuse localization causing headache, confusion, and somnolence. Focal stroke from thrombosis can also occur Vertigo, nystagmus, and ataxia Blurred vision, retinal hemorrhages, or central retinal vein thrombosis Dizziness Paresthesias, carpopedal spasm Secondary Complications: Emergency department presTreatment Complications: First line is reassurance and entation, which may be recurrent. Beta blockers and benzodiazepines are also used for refractory cases, with associated side effects of potential worsening of asthma and dependence/tolerance, respectively. Patients with acute hyperventilation presenting to an inner-city emergency department. Treatment Complications: Usual treatment with daily plasmapheresis carries risk of thrombosis and infection in often immunocompromised individuals. Hypocalcemia Epidemiology and Demographics: Relatively rare condition that is seen mainly in neonates or in patients with renal failure. Patients usually become symptomatic when serum calcium concentrations fall below 7. It is seen in conditions associated with hypoparathyroidism (primary or secondary), pseudohypoparathyroidism (parathyroid hormoneresistant syndromes), vitamin D deficiency, acute pancreatitis, or malabsorption syndromes. Severe acute hypocalcemia commonly occurs following thyroid or parathyroid surgery. Other causes of hypocalcemia include hypomagnesemia from alcohol use, vomiting, or poor oral intake. Hyperphosphatemia secondary to excessive oral or parenteral phosphate, tumor lysis syndrome, and rhabdomyolysis-induced acute renal failure can also lead to hypocalcemia. Medications such anticonvulsants and antimicrobials (foscarnet, pentamidine, and ketoconazole) can cause hypocalcemia. Risk factors include acute pancreatitis, hypoparathyroidism, vitamin D deficiency, and chronic kidney disease. Osteopetrosis, dental abnormalities, dry skin, coarse hair, and psoriasis in chronic untreated cases. Magnesium toxicity may lead to diminished deep tendon reflexes and intravenous calcium gluconate can be used as a useful antidote. Symptoms Localization site Cerebral hemispheres Comment Seizures (focal or generalized) nonresponsive to anticonvulsants, and pseudotumor cerebri Chronic hypocalcemia may result in headaches (secondary to increased intracranial pressure) and chorea or parkinsonism Irritability, confusion, agitation, mental dullness and intellectual disabilities, anxiety, delirium, delusions, hallucinations, psychosis, depression, and dementia Myelopathy secondary to vertebral lamina overgrowth Perioral paresthesia. Limb paresthesia (distal then spread proximally) Tetanic muscle contraction, which may progress to opisthotonos if truncal spasms occur. Carpopedal spasm Hypoglossal Nerve Palsy Epidemiology and Demographics: Prevalence is unknown. Disorder Description: the twelfth or hypoglossal nerve is a purely motor nerve controlling the extrinsic and intrinsic muscles of the tongue (except palatoglossus). Peripheral lesion could be due to head and neck tumor, internal carotid artery aneurysm or dissection, trauma, retropharyngeal abscess, or radiation therapy. Iatrogenic cases may follow internal jugular vein cannulation, carotid endarterectomy, and glomus jugulare resection. Motor neuron diseases, syringobulbia, tumor, and stroke may cause lesion to hypoglossal nucleus. Mental status and psychiatric aspects/ complications Spinal cord Peripheral neuropathy Muscle Symptoms Localization site Cranial nerves or cranial nerve nuclei Comment Ipsilateral tongue atrophy with tongue deviation toward the side of lesion. Difficulty in swallowing and talking, particularly in bilateral lesion Secondary Complications: Cataracts and papilledema. Basal 289 Section 1 Diagnostics Secondary Complications: Aspiration and malnutrition due to swallowing problem. Treatment Complications: Complication varies with treatment for each underlying cause. Hypoglycemia Epidemiology and Demographics: Hypoglycemia can occur in any age group. Disorder Description: the brain is very vulnerable to hypoglycemia because of the normally low concentration of glucose in the brain and its high cerebral metabolic rate. There are many causes of hypoglycemia secondary to the complexity of glucose homeostasis (insulin release, glycogen breakdown, and gluconeogenesis). It can result from conditions causing fasting hypoglycemia such as exogenous insulin, oral hypoglycemics, glucose overuse, elevated insulin levels, ketotic hypoglycemia, hypermetabolic state (sepsis), normal to low insulin levels, antibodies to endogenous insulin, excessive islet cell function (prediabetes, obesity), islet cell disorders (adenoma, cancer, nesidioblastosis), extrapancreatic tumors, and carnitine deficiency.

5 mg caduet sale. CoQ-10 blocks life-threatening side effects of cholesterol lowering meds.

Syndromes

• Multiple sclerosis
• Absence of part of the brain and skull (anencephaly)
• Burning of the mouth or the throat
• What medications do you take?
• Pregnancy
• Fainting or feeling light-headed

Primary insular carcinoid of the ovary with carcinoid heart disease: unfavourable outcome of a case cholesterol levels for child order caduet 5mg mastercard. Ventriculoperitoneal shunt for hydrocephalus caused by central nervous system metastasis cholesterol score calculator purchase caduet with a mastercard. Disorder Description: Causes can be pathogenic (congenital cholesterol kefir order caduet 5mg visa, acquired) or iatrogenic definition of cholesterol test order caduet 5mg with amex. They include myocardial infarction cholesterol control order caduet on line amex, structural heart disease cholesterol medication before blood test buy discount caduet line, coronary artery disease, thyroid abnormalities, substance-induced. Mononeuropathy or mononeuropathy multiplex Peripheral nerve Produces symptoms when lymphomas infiltrate Secondary Complications: Hydrocephalus, increased intracranial pressure, and associated symptoms Aseptic meningitis: mimics bacterial meningitis Acute/subacute encephalopathy: seizures, confusion, etc. Myelopathy Acute cerebellar syndrome Delayed leukoencephalopathy Symptoms Localization site Cerebral hemispheres Comment Cardioembolic or ischemic strokes leading to varying degrees of neurologic deficit. Emboli form in the heart as a result of turbulent blood flow or stasis and exit to the brain and other structures, causing blood vessel occlusion. Age, hypertension, and diabetes are important risk factors for the development of cardioembolic stroke. Vestibular system (and nonspecific dizziness) Symptoms Localization site Comment Large vessel cortical stroke Altered consciousness, loss of speech or memory, and hemineglect due to ischemic stroke Altered consciousness, diplopia, locked-in syndrome Cerebellar stroke, dysmetria and vertigo Vertigo Secondary Complications: Risk of intracerebral hemor- Cerebral hemispheres Mental status and psychiatric aspects/ complications Brainstem Cerebellum Vestibular system (and nonspecific dizziness) Cranial nerves Spinal cord rhage following ischemic stroke. Treatment Complications: Conversion of tachyarrhythmia to sinus rhythm carries risk of left atrial thrombus causing embolic phenomena. Patients receiving anticoagulation for stroke prevention are at increased risk of intracerebral hemorrhage. Secondary Complications: Rapid atrial fibrillation, limb Treatment Complications: Treatment of cardiac emboischemia, mesenteric ischemia. Cardioembolic stroke: clinical features, specific cardiac disorders and prognosis. Cardiac Embolus/Cardioembolic Stroke Epidemiology and Demographics: Approximately 20% of all ischemic strokes are of cardioembolic origin. Disorder Description: Cardiac embolism may occur in the setting of atrial fibrillation and mechanical and bioprosthetic heart valves without appropriate Cardiac Surgery Epidemiology and Demographics: Incidence of neurologic complications of cardiac surgery is estimated to be about 6%. Causes include cerebral hypoperfusion, atheroembolization, gaseous embolization, renal failure, hepatic failure, thyroid abnormalities, metabolic disturbances. Risk factors include hypertension, carotid disease, advanced age, previous stroke, and underlying pulmonary disease. Classic neurocardiogenic syncope is often linked to an identifiable trigger, such as an emotional stimulus. Genetics are thought to play a role in the "non-classical" neurocardiogenic syncope, which appears to be familial and without an identifiable trigger. The classical type most often occurs in the elderly and is associated with micturition, cough, defecation, and deglutition. Mechanistically, the reflex begins with a low blood pressure in the setting of blood pooling in the lower extremities, i. A sympathetic response ensues, with the heart appropriately responding by increasing the heart rate and stroke volume. Passing out allows one to be supine, which is thought to bring adequate blood supply to the brain in this position. Clinically, it is observed to occur in predisposed individuals following prolonged periods of upright posture, warm environments (hot weather, crowded rooms, hot shower/baths), pain, Symptoms Localization site Cerebral hemispheres Comment Ischemic, hemorrhagic stroke. Associated with poorer outcome compared with those cardiac surgery patients without a stroke Mental status and psychiatric Disturbances in memory, executive function, motor speed, aspects/complications attention, seizures, delirium, and coma Brainstem Cranial nerves Plexus Supranuclear gaze palsy (ischemic injury) Retinal infarctions, ischemic optic neuropathy (rare) Brachial plexus injury; numbness, weakness, pain, diminished reflexes, discoordination in upper extremity. Symptoms improve or resolve within 3 weeks (suggesting a neuropraxic injury caused by disruption of myelin sheath) Phrenic neuropathy; prolonged ventilator dependence Intercostal neuropathy (pain and dysesthesia in a localized distribution in the lateral chest wall) caused by harvesting of the internal thoracic artery Peripheral neuropathy Secondary Complications: Intracerebral hemorrhage sec- ondary to ischemic stroke. Treatment Complications: Risk of hemopericardium when antithrombotic therapy initiated for ischemic stroke. Symptoms Localization site Cerebral hemispheres Mental status and psychiatric aspects/ complications Comment Seizure-like activity may be seen, though this is nonepileptic Alterations in alertness, cognition, orientation, speech, memory, mood, anxiety; psychotic symptoms such as delusions or hallucinations, suicidal ideation. During the prodromal phase of the syncopal event, there may be an associated diaphoresis, pallor, disorientation, and nausea. Following the syncopal event, patients often express feeling depressed, delayed, fatigued, cloudy, light-headed, with difficulty concentrating. Fatigue is the most common complaint after an episode and may last for a number of days Recurrent dizziness (prodromal or post-syncope) Diffuse muscle aches, pain Headache Carotid Artery Aneurysm Epidemiology and Demographics: An estimated 3. Risk of intracranial aneurysm increases with a positive family history or in patients with autosomal dominant polycystic kidney disease and connective tissue disease. Disorder Description: Aneurysms are abnormal dilations of a blood vessel wall that arise due to defects, disease, or injury to the vessel. The majority of carotid aneurysms occur intracranially at the bifurcation of the internal carotid and posterior communicating artery but can occur in the cervical carotid, especially as a result of trauma. Aneurysms may be saccular (sac-like protrusion from the vessel) or fusiform (involving entire circumference of involved vessel). Other considerations for treatment include cardiac pacing or closed loop stimulation, volume maintenance therapies, i. Mental status and psychiatric aspects/complications Brainstem Cranial nerves Bibliography Chen-Scarabelli C. Treatment Complications: Treatment of unruptured aneurysms by procedural intervention is possible; however, there is an associated risk of morbidity and mortality. Overall, small unruptured carotid artery aneurysms typically do not warrant intervention; for larger aneurysms, intervention should be considered based on aneurysm size, symptoms, age, and functional status of the patient. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and metaanalysis. Carotid Artery Dissection Epidemiology and Demographics: Incidence of spontaneous carotid artery dissection is 1. Patients with connective tissue disorders are at increased risk of spontaneous dissection. Disorder Description: Dissection is caused by the tearing or separation of arterial wall layers. It occurs after the formation of a tear in the tunica intima layer of the artery, allowing arterial blood to enter into the vessel wall. These subintimal dissections cause stenosis or possibly occlusion of the vessel and increase the risk of thrombus formation, which may embolize distally. Transient ischemic attack and acute ischemic stroke are possible, which can have permanent consequences depending on severity, duration, and location of ischemia. Treatment Complications: Treatment depends on location and severity of dissection. In cases of thrombus, anticoagulation is often used, complications of which include bleeding. Angioplasty or stenting can be done in case of failed medical management and have lower risk of complication compared with surgical treatment but may cause stroke. Carotid Artery Endarterectomy or Stent Epidemiology and Demographics: Carotid artery endarterectomy and stenting are both utilized in patients with carotid artery stenosis for prevention of stroke, which is currently the fourth leading cause of death in the United States and where 20% of strokes are secondary to carotid artery stenosis. In patients with asymptomatic carotid artery stenosis, the risk of ipsilateral stroke is 0. In symptomatic patients with less than 70% stenosis, intervention has questionable benefit compared with medical treatment and carries risks. In patients with asymptomatic carotid atherosclerosis, intervention can be considered if stenosis is greater than 60%. Carotid atherosclerosis can cause symptoms either by decreased flow due to stenosis or artery-to-artery embolism. Symptoms Localization site Cerebral hemispheres Comment Transient ischemic attacks, stroke: can present as focal deficits such as sudden weakness, numbness, difficulty speaking, etc. Hemiparesis, aphasia, neglect; headache Confusion, altered mental status, or loss of consciousness Amaurosis fugax. Disorder Description: the internal carotid artery forms a fistula with the cavernous sinus, shunting blood away from the brain and into the venous circulation. The higher arterial blood pressure subjects the wall of the cavernous sinus to substantial mechanical forces. Mental status and psychiatric aspects/complications Visual system Vestibular system (and nonspecific dizziness) Cranial nerves Diplopia, dysarthria Treatment Complications: When indicated, both carotid endarterectomy and stenting have been proved beneficial overall, although complications can occur. In terms of primary outcomes of stroke, myocardial infarction and death, endarterectomy and stenting appear to have similar risks of adverse outcomes. Perioperatively, stenting is associated with higher risk of stroke, while endarterectomy is associated with higher risk of myocardial infarction. Hyperperfusion syndrome can occur after carotid artery stenting or endarterectomy and is characterized by severe headache and hypertension. Patients who develop hyperperfusion syndrome often had diagnoses of very severe or bilateral stenosis. Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: risk factors, prevention, and treatment. Treatment Complications: In most settings, the current preferred treatment is endovascular embolization. Embolization carries the risk of cerebral infarction, diabetes insipidus, decreased visual acuity, orbital ecchymosis, retroperitoneal hematoma, and deep vein thrombosis. Traumatic carotid cavernous fistula accompanying basilar skull fracture: a study on the incidence of traumatic carotid cavernous fistula in the patients with basilar skull fracture and the prognostic analysis about traumatic carotid cavernous fistula. Dural carotid cavernous fistula: definitive endovascular management and long-term follow-up. A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. The patients present with pain, paresthesia, numbness, and possible weakness in the median nerve distribution. The median nerve emerges from the fifth cervical to the first thoracic roots, but is mainly formed from the sixth cervical root. The median nerve supplies four muscles in the forearm (pronator teres, flexor carpi radialis, palmaris longus, and flexor digitorum superficialis). Within the tunnel is the tendon of the flexor pollicus longus and four tendons of the flexor digitorum superficialis and profundus muscles. The motor branch usually supplies the abductor pollicus brevis, opponens pollicis, and the first and second lumbrical muscles (sometimes the flexor pollicus brevis muscle). The palmar cutaneous nerve arises proximal to the carpal tunnel and supplies the skin over the thenar eminence. Anatomical compression and/or inflammation are the most common causes of carpal tunnel syndrome. Risk factors include repetitive use of the hand, obesity, female gender, pregnancy, diabetes mellitus, rheumatoid arthritis, hypothyroidism, and workplace factors. Carotid Sinus Hypersensitivity Epidemiology and Demographics: Incidence is related to age; prevalence is 2. Disorder Description: Carotid sinus hypersensitivity is defined as a decrease in heart rate (at least 3-second asystole, "cardioinhibitory type") or blood pressure (>50 mmHg systolic pressure drop, "vasodepressor type") or both ("mixed type") in response to carotid sinus massage. Syncope and near syncope, provoked by head turning, a tight collar, or shaving, are the most common presentations. Pathogenesis may be related to carotid sinus atherosclerosis, sternocleidomastoid proprioceptive denervation, or autonomic dysfunction. Symptoms Localization site Mental status and psychiatric aspects/complications Comment Recurrent syncope, near syncope, light-headedness Secondary Complications: this condition can cause falls Treatment Complications: Treatment involves placement in the elderly. Risks for this procedure include palpitations, infection, bleeding, pacemaker lead dislodgement, and pacemaker malfunction. Treatment of underlying condition if present, such as rheumatoid arthritis and hypothyroidism, is usually helpful. Treatment for severe cases is decompression of the median nerve at the carpal tunnel. Symptoms Localization site Peripheral neuropathy/ mononeuropathy Muscle Comment Median nerve distribution sensory and motor symptoms Atrophy of abductor pollicis brevis and even death. Interestingly, although other forms of cyanide poisoning have been shown to cause basal ganglia damage and parkinsonism with severe toxicity, this has not been reported with cassava root poisoning, probably because those stricken do not survive. Tropical ataxic neuropathy develops slowly as a result of chronic consumption of cassava root and is associated with sensory loss in the lower extremities and optic atrophy. Interestingly the cyanide exposure is higher in konzo than in tropical ataxic neuropathy, and the onset is abrupt. Symptoms Localization site Cerebral hemispheres Comment Konzo causes upper motor neuron damage with spastic paraparesis. Rarely, there may also be spastic dysarthria, but it usually resolves Optic atrophy with tropical ataxic neuropathy Tropical ataxic neuropathy causes distal sensory loss Treatment Complications: Oral glucocorticoid treatment should not extend beyond 4 weeks due to deleterious side effects of chronic therapy.