Neurology

·         Although episodes of vertigo associated with Meniere syndrome usually last from hours to a day, deafness is constant after it develops. The deafness is characterized initially by a compromised ability to hear low-frequency sounds. Tumarkin otolithic crisis is a sudden spell of falling to the ground associated with Meniere syndrome. Meniere syndrome can be associated with nausea and vomiting.

·         Episodes of vertigo in middle-aged patients should prompt consideration of vertebrobasilar insufficiency as a cause. The vertigo can represent transient ischemic attacks, which are warning signs of possible vertebrobasilar occlusion, a life-threatening condition.

·         Vestibular neuritis is quite common, second only to BPPV as a cause of vertigo in most dizziness clinics. It is frequently associated with an upper respiratory tract infection and usually lasts from days to weeks. Hearing is uniformly preserved.

·         The severity of the diabetic polyneuropathy correlated more closely with the degree of hyperglycemia (mean glycosylated hemoglobin) than with the duration of diabetes. ( cf: in retinopathy, its duration.)

·         Malignant hyperthermia is an autosomal dominant disorder caused by a defect on chromosome 19q13, leading to a mutation of the ryanodine receptor (RyR) gene. Mutations of RyR cause accelerated calcium release from the sarcoplasmic reticulum during general anesthesia with compounds such as halothane, ether, and succinylcholine. This leads to a rapid increase in metabolism, dramatic elevations of body temperature, acidosis, muscle rigidity, myoglobinuria, and death. A careful family history may give clues to the diagnosis and should prompt referral for a muscle biopsy and in vitro caffeine-halothane contraction testing. Patients with malignant hyperthermia can usually safely undergo anesthesia with nitrous oxide, thiopental, and nonpolarizing muscle relaxants. I.V. dantrolene is effective if administered early in the disease course, but patients who develop the syndrome still have a 7% mortality.

·         Hyperkalemic periodic paralysis is caused by a defect of the sodium channel, precipitated by rest following exercise, stress, potassium administration, and the ingesting of certain foods. Hypokalemic periodic paralysis is caused by a defect in the calcium channel and is precipitated by the partaking of meals high in carbohydrates, rest following exercise, and excitement. If the potassium level is found to be low during attacks, secondary causes of hypokalemia (diuretics, hyperaldosteronism, laxatives, etc.) or thyrotoxicosis (especially in patients of Asian descent) should be sought. A serum potassium level that is elevated without apparent cause is suggestive of hyperkalemic periodic paralysis.

·         Noncontrast CT reliably distinguishes acute intracerebral hemorrhage from ischemia. This distinction is critical because the management of hemorrhagic stroke is substantially different from that of ischemic stroke.

·         ICH volume and consciousness level are the two most powerful predictors of outcome in ICH. Observations suggest that about one third of ICHs expand in the first 24 hours. Some investigators have juxtaposed this fact with a need to lower blood pressure in acute ICH. Because it has been shown to improve outcome, nimodipine, a calcium channel blocker, is begun on the first day and continued for 21 days.

·         MTBI (mild traumatic brain injury) is defined as any traumatic brain injury/concussion with loss of consciousness of 0 to 30 minutes, a GCS score of 13 to 15 on admission, posttraumatic amnesia or confusion lasting less than 24 hours, and no evidence of contusion or hematoma on CT.

·         Corticosteroids should not be used for neuroprotection or control of ICP in patients with severe TBI.

·         The risk of epilepsy in patients with closed-head injury is relatively small: 2% to 5% in all patients and about 10% to 20% in patients with severe closed-head injury. A higher incidence of seizures has been seen in patients with depressed skull fractures (15%), hematomas (31%), and penetrating brain wounds (50%).

Because most patients who develop posttraumatic epilepsy in the first week after injury will have recurrent seizures for some time, anticonvulsant therapy is indicated in documented cases. Controlled, randomized studies have shown that the use of phenytoin, phenobarbital, carbamazepine, and valproate do not prevent the development of posttraumatic epilepsy beyond the first week after injury.

·         As with other metastatic tumors, breast cancer tends to produce multiple lesions that are most commonly located at the junction of the white matter and gray matter.

Of interest, women with breast cancer are known to have an increased incidence of meningiomas. Prognosis of meningiomas is in general excellent; surgical excision tends to be curative.

·         The peripheral nervous system is affected by two different sets of antibodies. Both peripheral neuropathies are predominantly sensory. In patients with lymphoma and Waldenström disease, myelin-associated glycoprotein antibodies (anti-MAG) are produced. Anti-Hu antibodies are found in patients with peripheral neuropathy and encephalomyelitis associated with small cell carcinoma of the lung.

Because of the clear relationship between ovarian cancer and paraneoplastic cerebellar degeneration due to anti Yo antibodies.

·         The persistent vegetative state is characterized by the return of sleep-wake cycles and of various reflex activities, but wakefulness is without awareness. Recent studies have indicated that the minimally conscious state, which is characterized by inconsistent but clearly discernible behavior of consciousness, can be distinguished from coma and a vegetative state by the presence of behavioral conditions not found in either of those two conditions; this distinction is important because outcome appears to be different in minimally conscious patients. Brain death is defined as the loss of all cerebral activity, including activity of the cerebral cortex and brain stem, for at least 6 hours if confirmed by electroencephalographic evidence of electrocerebral inactivity or for 24 hours without a confirmatory electroencephalogram.

·         Thiamine replacement therapy rarely leads to improvement in Korsakoff’s Psychosis.

·         Chronic daily headache (CDH) includes four different headache types: transformed migraine, chronic tension-type headache, hemicrania continua, and new drug persistent headache.

·         Friedreich ataxia is the most common recessively inherited ataxia. Patients often present before the age of 25 years with ataxia. Other symptoms can include dysarthria, vision problems, weakness, and dysphagia. Physical examination reveals loss of deep tendon reflexes, poor proprioception, weakness, and extensor plantar response. Phenotypic variation is not uncommon, and some patients have preserved or brisk deep tendon reflexes. Between 30% and 50% of patients develop symptomatic heart disease, including hypertrophic cardiomyopathy.

·         The longer-acting agent clonazepam may be a better choice for depression in AD. Buspirone is another alternative for the treatment of anxiety in AD patients. Treatment of agitation generally requires antipsychotics. Quetiapine has the significant advantage of being much less likely to induce extrapyramidal signs than both newer and older agents.

·         Patients with DLB often experience marked fluctuations in their alertness and level of arousal from one day to the next. They often sleep excessively. In RBD, patients engage in dream enactment, thrashing about in bed or talking in their sleep. RBD can often precede the dementia and the movement disorder by years and is highly specific for DLB.

·         Two medications that often cause cognitive dysfunction: amitriptyline (a tricyclic antidepressant with anticholinergic activity) and lorazepam (a benzodiazepine). These medications should be changed or discontinued before considering the diagnosis of a primary dementia syndrome.

·         Pseudoseizures; currently, the preferred term for such seizures is nonepileptic seizures. Use of this term tends to help the patients understand their problem and facilitates referral for behavioral therapy. An important clue to the diagnosis of nonepileptic seizures is that they are periodic events that tend not to be stereotyped. Both patients and observers report varied behaviors with each event. Another clue is the prolonged duration. Nonepileptic seizures may last 30 minutes to several hours—longer than typical seizures. Patients with both nonepileptic seizures and epilepsy pose a challenging problem; this combination is occasionally found in patients undergoing assessment in epilepsy monitoring units.

·         Narcolepsy is a disorder of unknown etiology. A strong association exists between narcolepsy and the presence of the DR-15 subtype of DR2 and the DQB1*0602 subtype of DQw1 haplotypes. The most exciting recent development in our understanding of narcolepsy is the documentation of an abnormality in the hypocretin neurons in the lateral hypothalamus. Human narcolepsy-cataplexy can be considered a hypocretin (orexin) deficiency syndrome.

·         Partial arousal disorders include confusional arousals, sleepwalking (somnambulism), and sleep terrors (pavor nocturnus). These conditions are a subset of the parasomnias: disorders that occur during the sleep-wake transitions and during partial arousals. Parasomnias are characterized by abnormal movements or behaviors that intrude into sleep without disturbing sleep architecture. An overnight sleep study with simultaneous video recording can confirm unusual movements or behavior during nighttime sleep in patients with parasomnias. Most partial arousal disorders are benign.

·          Pain is a subjective experience, and its expression is unique to each patient. Often there is little objective evidence with which to assess the source or intensity of pain. Thus, one of the most important aspects of the patient-physician relationship regarding the treatment of chronic pain is trust: the physician is obligated to rely on the patient’s self-reports of pain; to do otherwise may be unethical. Pain is a complex process that involves biologic and psychosocial factors.

·         In patient with a known seizure disorder, a combination of acetaminophen and codeine is a safe choice for short-term treatment of pain. Tramadol, a nonnarcotic analgesic that binds to mu opiate receptors in the CNS and causes inhibition of ascending pain pathways, is contraindicated in this patient because it tends to make seizures worse. Similarly, tricyclic antidepressants and the opioid analgesic meperidine can induce seizures and thus would not be the best initial choice.

·         The combination of parkinsonism, autonomic insufficiency, and ataxia is strongly suggestive of multiple systems atrophy.

·         HSV-2 is the primary cause of benign recurrent lymphocytic meningitis. Unlike viral meningitides that have a seasonal association, HSV-2 meningitis occurs at any time of year. The typical symptoms and signs are headache, fever, stiff neck, and a marked lymphocytic pleocytosis in the CSF.

·         Unlike most viral encephalitides, HSV-1 encephalitis is focal. HSV replication in the medial temporal lobe and orbital surface of the frontal lobe, with accompanying inflammation, produces the characteristic clinical picture. Fever, headache, lethargy, irritability, and confusion are typical symptoms. Seizures (major motor, complex partial, focal, and even absence attacks) affect approximately 40% of patients. If the dominant temporal lobe is involved, aphasia and focal motor or sensory deficits develop. The CSF is usually abnormal in HSV encephalitis.

Although RBCs are unusual in other viral encephalitides, in HSV encephalitis they are often present in the CSF, which may also be xanthochromic; this presumably reflects the hemorrhagic nature of brain lesions. Instead of attributing the presence of RBCs in CSF to a so-called traumatic tap, the astute clinician may use this finding to support the presumptive diagnosis of HSV encephalitis.

·         Radiologic findings can be similar in HAM and multiple sclerosis. Both diseases can cause elevated IgG and oligoclonal bands in the CSF. Although HAM is reported mainly in Japan, the Caribbean region, and Central America, it does occur in the southeastern United States. HTLV-I can also cause a T cell lymphoma/leukemia, and although it is rare to have the neurologic and hematopoietic complications occur at the same time, this patient’s skin biopsy is characteristic of a cutaneous lymphoma. Serology testing should be done to confirm HTLV-I infection.

Remember that in MS, the total protein concentration Iis usually normal; however, Ig levels are high relative to other protein components. The predominant Ig is IgG, although IgM and IgA are also increased. The IgG index is used to measure the increase in IgG levels relative to other proteins. Also CSF pressure is normal, protein is normal, and cell count is normal.

·         Variant CJD is believed to be the accidental transmission to humans of the agent of bovine spongiform encephalopathy (mad cow disease). It differs from CJD in that it occurs in younger patients. Patients present with psychiatric disturbances; dementia develops much later. Patients with CJD lack characteristic EEG findings and have a longer survival time. This patient had classic findings of CJD: visual changes, dementia, ataxia, myoclonic jerks, a characteristic EEG study, and rapid progression to death.

·         On MRI, the lack of contrast enhancement is typical for PML, as distinct from toxoplasmosis, lymphoma, or astrocytoma. Bizarre cells are seen on biopsy but do not indicate the presence of a malignancy. The intranuclear inclusions in the oligodendrocytes are typical for PML. There are no proven therapies of benefit in managing PML, although it is believed that partial reversal of the immunodeficient state may be responsible for transient improvement.

·         Nonsteroidal anti-inflammatory drugs can cause a meningoencephalitis, especially in patients with underlying collagen vascular diseases.

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·         Cerebellar problems can present as three diseases:

Ataxia – telangiectasia

• Telangiectasia all over skin
• lady with spider veins
• Have IgA deficiencies
• diarrhea, respiratory illness

Fredriechs Ataxia

• Retinitis pigmentosa (pigments on the retina)
• Scoliosis (5-10%)

Adrenoleukodystropy

• adrenal gland is knocked out
• electrolyte problems
• Long chain fatty acids accumulation in the mitochondria (transferred by carnitine)
• Involvement of Cortex early on
• spasticity
• babinsky

·         Gerstmann–Sträussler–Scheinker syndrome (GSS) is a very rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age. This extremely rare disease is classified as a transmissible spongiform encephalopathy.

GSS is one of a small number of diseases which are caused by prions, a class of pathogenic proteins highly resistant to proteases.

Symptoms start with slowly developing dysarthria (difficulty speaking) and cerebellar ataxia (unsteadiness) and then the progressive dementia becomes more evident.

There is no cure or treatment for GSS and patients rarely survive longer than five years.

·         Neuroblastoma is the most common extracranial solid tumor in infancy. It is an embryonal malignancy of the sympathetic nervous system arising from neuroblasts (pluripotent sympathetic cells). undifferentiated neuroblastomas histologically present as small, round, blue cell tumors with dense nests of cells in a fibrovascular matrix and Homer-Wright pseudorosettes. These pseudorosettes, which are observed in 15-50% of tumor samples, can be described as neuroblasts surrounding eosinophilic neuritic processesA neuritic process, also called neuropil, is a pathognomonic feature of neuroblastoma cells.

Shimada histopathologic classification system

Important features of the classification include (1) the degree of neuroblast differentiation, (2) the presence or absence of Schwannian stromal development (stroma-rich, stroma-poor), (3) the index of cellular proliferation (known as mitosis-karyorrhexis index [MKI]), (4) nodular pattern, and (5) age.

Joshi histopathologic classification system

This system classifies tumors based on the presence of calcification and mitotic rate, as follows: (1) good prognosis (ie, low mitotic rate and calcification), (2) intermediate prognosis (ie, low mitotic rate or calcification), and (3) poor prognosis (ie, high mitotic rate and no calcification).

·         Mutations affecting nonmuscle myosin heavy-chain type II-A results in MYH9-related hereditary macrothrombocytopenia syndromes, including 4 autosomal dominant platelet disorders (ie, Fechtner syndrome, Epstein syndrome, May-Hegglin syndrome, and Sebastian syndromes).

Epstein's syndrome is defined as a subtype of Alport's syndrome, and is distinguished from the other subtypes by accompanying macrothrombocytopenia.

Epstein's syndrome is a rare inherited disorder that appears principally as nephritis and deafness with thrombocytopathic thrombocytopenia producing a bleeding tendency. An association between hereditary nephritis, deafness, and megathrombocytopenia is reported as part of 2 distinct syndromes.

Fechtner syndrome consists of nephritis, sensorineural hearing loss, cataracts, macrothrombocytopenia, and characteristic polymorphonuclear inclusion bodies. Epstein syndrome is similar to Fechtner syndrome but without neutrophilic inclusions. Transmission appears to be autosomal dominant in both syndromes.

·         Anton-Babinski syndrome, is a rare symptom of brain damage occurring in the occipital lobe. People who suffer from it are "cortically blind," but affirm, often quite adamantly and in the face of clear evidence of their blindness, that they are capable of seeing. Failure to see is dismissed by the sufferer through confabulation.

·         The presence of anti-Jo-1 antibody in patient of PM/DM is a marker for interstitial lung disease.

·         Guillain-Mollaret triangle: This is not an anatomical triangle but a triangular circuit connecting the dentate nucleus of the cerebellum of one side with the red nucleus and the inferior olive on the other side, via the superior cerebellar peduncle, the central tegmental tract, and the inferior cerebellar peduncle.

·         In TBME, CN palsies may be either unilateral or bilateral and most commonly occur in CN VI (abducens, usually bilateral). Palsies may also develop in CN III (oculomotor) > CN IV (trochlear) > CN II (optic).

·         Viral encephalitis is caused by a number of arboviruses belonging to the families Flaviviridae, Togaviridae, Bunyaviridae, and Reoviridae; other zoonotic viruses can also cause viral encephalitis. Almost all viruses that cause encephalitis are transmitted by either mosquitoes or ticks. Of those transmitted by mosquitoes, the majority have a bird vertebrate host. The exceptions are the encephalitides caused by Bunyaviridae, which include La Crosse encephaliti (rodent host)s; California encephalitis; some viruses of the Togaviridae family, including Venezuelan equine encephalitis; and some cases of Western equine encephalitis. St. Louis encephalitis, West Nile encephalitis, and Murray Valley encephalitis are all transmitted by mosquitoes that have birds as their vertebrate host.

·         With an incidence of 180 per 100,000 people, MTBI is more common than any other neurologic diagnosis except migraine. MTBI is defined as any traumatic brain injury/concussion with loss of consciousness of 0 to 30 minutes, a GCS score of 13 to 15 on admission, posttraumatic amnesia or confusion lasting less than 24 hours, and no evidence of contusion or hematoma on CT. Although the emergency department evaluation and management of MTBI is controversial, the principal concern is with identifying evolving surgical lesions such as hematomas and contusions. In addition to history and examination, CT has become the mainstay of evaluation. Prolonged or deteriorating mental status or the presence of neurologic signs or other risk factors are still indications for CT scanning, observation, or both after MTBI. MRI promises to be very useful in the long-term management of moderate and severe TBI, as well as in the documentation of brain pathology in patients with milder injury. However, it is often impractical and not cost-effective in the acute setting. This patient has MTBI, and observation for a few hours and possibly a CT scan to rule out contusions are appropriate. He does not have severe enough trauma to warrant admission or invasive monitoring of his ICP.

·         Acanthocytes are seen in abetalipoproteinaemia. Retinitis pigmentosa is seen in abetalipoproteinaemia. Mental retardation is not present but motor abnormalities and neurodegenerative are seen.