IM Neurology 1 (3) PDF

Neurology 1 PHAS 6340: INTERNAL MEDICINE  Huntington Disease Gradual onset and progression of chorea and dementia or behavioral change Inherited in an autosomal dominant manner and occurs throughout the world  Huntington Disease Etiology is Genetic: ...

Neurology 1 PHAS 6340: INTERNAL MEDICINE  Huntington Disease Gradual onset and progression of chorea and dementia or behavioral change Inherited in an autosomal dominant manner and occurs throughout the world  Huntington Disease Etiology is Genetic:  Inherited in an autosomal dominant manner and occurs throughout the world  The gene responsible for the disease has been located on the short arm of chromosome 4 Huntington Disease Symptoms May consist of either abnormal movements or intellectual changes However, both ultimately occur Earliest mental changes Often behavioral, with irritability, moodiness, antisocial behavior, or psychiatric disturbance However, a more obvious dementia subsequently develops Huntington Disease Dyskinesia May initially be no more than an apparent fidgetiness or restlessness However, choreiform movements and some dystonic posturing eventually occur A parkinsonian syndrome with progressive rigidity and akinesia (rather than chorea) sometimes occurs in association with dementia, especially in cases with childhood onset  Huntington Disease Diagnosis: Genetic testing permits presymptomatic detection and definitive diagnosis of the disease Offspring of patients diagnosed with Huntington’s disease should be offered genetic counseling Huntington Disease  Imaging Studies CT scanning or MRI usually demonstrates cerebral atrophy and atrophy of the caudate nucleus in established cases Positron emission tomography (PET) has shown reduced striatal metabolic rate Huntington Disease Prognosi Treatment s Dopamine receptor There is no cure for Huntington blockers, such as disease phenothiazines or Progression cannot be halted haloperidol, may control Treatment is purely the dyskinesia and any symptomatic behavioral disturbances The disease is usually fatal within 15–20 years  Huntington Disease Management  Allpatients should be referred to neurology and, ultimately, to one of the 50 U.S. Huntington's Disease Centers of Excellence Multi-disciplinary care teams that have expertise in Huntington disease All share an exemplary commitment to providing comprehensive care Myastheni a Gravis Fluctuating weakness of voluntary muscles The external ocular muscles and certain other cranial muscles, including the masticatory, facial, and pharyngeal muscles, are especially likely to be affected Myasthenia Gravis Pathophysiology Symptoms are due to blocks of neuromuscular transmission caused by autoantibodies binding to acetylcholine receptors Can be associated with the presence of a thymoma  Myasthenia gravis Symptoms: Weakness  May remain localized to a few muscle groups, especially the ocular muscles  May become generalized Myasthenia Gravis  Symptoms often fluctuate in  The bulbar and limb muscles are intensity during the day often weak, but the pattern of  involvement is variable Sustained activity of  affected muscles increases Bulbar (oropharyngeal) weakness  the weakness, which Fatigue with prolonged improves after a brief rest chewing   Dysphagia Respiratory muscle weakness may lead to  Dysphonia respiratory failure  Dysarthria (Myasthenia crisis) Myasthenia Gravis Physical exam Diagnosis  Sensation is normal  Initial test of choice is  Acetylcholine receptor Usually no reflex changes antibody assay  Ice pack test  Repetitive nerve stimulation  Applicationof ice pack (electrophysiology) and single for 10 minutes fiber electromyography improves ocular (SFEMG) are the most acute symptoms tests  Myasthenia Gravis  Long term Treatment  Acetylcholinesterase inhibitors provide symptomatic relief (first line option)  Neostigmine  Pyridostigmine  Treatment of severe disease or Myasthenic crisis  IVIG (intravenous immunoglobulin)  Plasmapheresis  Myasthenia Gravis  Surgery  Thymectomy  Usuallyleads to symptomatic benefit or remission  Should be considered in all patients younger than age 65 unless weakness is restricted to the extraocular muscles  Avoid medications known to worsen MG  Aminoglycosides, Fluoroquinolones, Beta Blockers Lambert-Eaton Myasthenic syndrome Defective release of acetylcholine in response to a nerve impulse, leading to weakness, especially of the proximal muscles of the limbs Lambert-Eaton Myasthenic syndrome May be associated with small-cell carcinoma, sometimes developing before the tumor is diagnosed, and occasionally occurs with certain autoimmune diseases Lambert-Eaton Myasthenic syndrome Clinical findings Diagnosis Variable weakness, typically improving with  Electrophysiologic activity testing Dysautonomic symptoms may also be  Serological present A history of malignant disease may be testing P/Q type obtained voltage-gated Unlike myasthenia gravis, power steadily calcium channel increases with sustained contraction antibody assay  Lambert-Eaton Myasthenic syndrome Treat the underlying malignancy Symptomatic management Amifampridine IVIG/ plasmapheresis Encephalitis  Encephalitis is defined as an inflammation of the brain caused either by infection, usually with a virus, or from a primary autoimmune process.  Similar to meningitis, encephalitis is typically an acute febrile illness.  The patient with encephalitis commonly has an altered level of consciousness (confusion, behavioral abnormalities), or a depressed level of consciousness ranging from mild lethargy to coma, and evidence of either focal or diffuse neurologic signs and symptoms. Encephalitis  Virtually every possible type of focal neurologic disturbance has been reported in viral encephalitis; the signs and symptoms reflect the sites of infection and inflammation.  Patients with encephalitis may have hallucinations, agitation, personality change, behavioral disorders, and, at times, a frankly psychotic state. Focal or generalized seizures occur.  Encephaliti s Hundreds of viruses are capable of causing encephalitis, although only a limited subset is responsible for most cases in which a specific cause is identified. Herpes Simplex Virus 1 is the most commonly identified virus Some commonly identified Viruses * HSV1, HSV2, Human herpes virus 6 West Nile virus HIV, Cytomegalovirus, Epstein-Barr St Louis encephalitis virus virus Varicella-zoster virus Zika Enteroviruses La Crosse virus Arthropod-borne viruses  Encephalitis  Physical exam  Focal neurological deficits Hemiparesis Sensory deficits Cranial nerve palsies Exaggerated deep tendon reflexes Myoclonus Tremor Ataxia  Encephaliti s  Diagnosis  Lumbar puncture:  The characteristic CSF profile is indistinguishable from that of viral meningitis and typically consists of a lymphocytic pleocytosis, a mildly elevated protein concentration, and a normal glucose concentration.  PCR testing of CSF can identify the cause  CT scan should be performed to rule out space occupying lesions  Encephaliti s  Vital functions, including respiration and blood pressure, should be monitored continuously and supported as required. In the initial stages of encephalitis, many patients will require care in an intensive care unit.  Acyclovir is of benefit in the treatment of HSV and should be started empirically in patients with suspected viral encephalitis, especially if focal features are present, while awaiting viral diagnostic studies. Encephalopathies Encephalopathies Encephalopathy refers to altered brain function in the absence of inflammation. Encephalitis is an infection of the brain parenchyma predominantly caused by viruses. Encephalopathies Common manifestations of encephalopathy include confusion, personality changes, disorientation, aphasia, delirium, and dementia. In general, patients with encephalopathy do not have fever, headache, seizures, focal neurologic signs, and an increased wbc count in the blood and spinal fluid, whereas patients with encephalitis often do. Encephalopathies Common manifestations of encephalopathy include confusion, personality changes, disorientation, aphasia, delirium, and dementia. In general, patients with encephalopathy do not have fever, headache, seizures, focal neurologic signs, and an increased wbc count in the blood and spinal fluid, whereas patients with encephalitis often do.  Hepatic Encephalopathy  A state of disordered central nervous system function resulting from failure of the liver to detoxify noxious agents of gut origin because of hepatocellular dysfunction and portosystemic shunting  Generally occurs in patients with cirrhosis or acute liver failure (sometimes both)  Hepatic Encephalopathy  Ammonia is the most readily identified toxin but is not solely responsible for the disturbed mental status  Hepatic Encephalopathy  Precipitants of hepatic encephalopathy Gastrointestinal (GI) bleeding— increases protein in the bowel and rapidly precipitates hepatic encephalopathy Constipation Alkalosis Potassium deficiency induced by diuretics  Hepatic Encephalopathy  Precipitants of hepatic encephalopathy Opioids, hypnotics, and sedatives Medications containing ammonium or amino compounds Paracentesis with consequent hypovolemia Hepatic or systemic infection Portosystemic shunts  Hepatic Encephalopathy  Signs Day–night reversal Asterixis, tremor, dysarthria Delirium Drowsiness, stupor, and ultimately coma  Hepatic Encephalopathy  Diagnosis: Liver biochemical tests often consistent with advanced chronic liver disease Serum (and cerebrospinal fluid) ammonia level is generally elevated  Ultimately a clinical diagnosis supported by asterixis, elevated serum ammonia with exclusion of other causes of delirium  Hepatic Encephalopathy  Treatment  Lactulose in most patients  Withhold dietary protein during acute episodes  If due to GI bleeding  Purge blood from the GI tract with 120 mL of magnesium citrate by mouth or nasogastric (NG) tube every 3–4 hours until the stool is free of gross blood  Hepatic Encephalopathy  Prevention of reoccurrence: When the patient resumes oral intake, protein intake should be restricted to 60–80 g/day as tolerated, and vegetable protein is better tolerated than meat protein Continued use of lactulose after an episode of acute encephalopathy reduces the frequency of recurrences   This is a special type of nonicteric hepatic encephalopathy occurring in Reye children and adolescents and characterized by acute brain Syndrome swelling in association with fatty infiltration of the viscera, AKA Reye-Johnson particularly the liver. syndrome  Rare but very dangerous encepholapthy with a mortality rate of 21%   The cause is unknown but may be related to viruses, vaccines, Aspirin and possibly congenital metabolic disorders. Reye  Illness begins with protracted Syndrome vomiting and delirium, which progresses to coma within 2 AKA Reye-Johnson syndrome days. Seizures are common but are usually self-limited.  Sustained hyperventilation and hepatomegaly are usually noted.  Wernicke Encephalopathy  Wernicke encephalopathy is characterized by confusion, ataxia, and nystagmus leading to ophthalmoplegia (lateral rectus muscle weakness, conjugate gaze palsies); peripheral neuropathy may also be present.  It is due to thiamine deficiency and in the United States occurs most commonly in patients with alcohol use disorder.  Wernicke Encephalopathy  In suspected cases, thiamine (100 mg) is given intravenously immediately and then intramuscularly on a daily basis until a satisfactory diet can be ensured after which the same dose is given orally.  The diagnosis is confirmed by the response in 1 or 2 days to treatment, which must not be delayed while awaiting laboratory confirmation of thiamine deficiency from a blood sample obtained prior to thiamine administration.  Korsakoff Syndrome  Occurs in more severe cases of Wernicke encephalopathy  It includes anterograde and retrograde amnesia and sometimes confabulation and may not be recognized until after the initial delirium has lifted. Chronic traumatic encephalopathy  Chronic traumatic encephalopathy (CTE) is a disease that causes brain tissue to break down over time.  Repeated head injuries have caused all cases of CTE so far. Anoxic encephalopathy  Anoxic encephalopathy, or  Common causes: hypoxic-ischemic brain  carbon monoxide poisoning injury, is a process that  drug overdose begins with the cessation of  vascular injury or insult cerebral blood flow to brain tissue  cardiac arrest Hypercapnic pulmonary disease Diseases of the lungs or medullary respiratory centers cause permanent respiratory acidosis.  Symptoms:  headache, papilledema, mental dullness, drowsiness, confusion, stupor and coma, and asterixis  Prognosis  Unlike pure hypoxic encephalopathy, prolonged coma because of hypercapnia is relatively rare and unlikely to lead to irreversible brain damage. Hypertensive encephalopathy One of the types of end organ damage in hypertensive emergency Without treatment, there may be cerebral ischemia, hemorrhage, or both, with focal cerebral symptoms or signs. Hypertensive encephalopathy Hypertensive encephalopathy is one of several forms of posterior reversible encephalopathy syndrome (PRES), a syndrome also encompassing other etiologies, including renal failure, immunosuppressive therapy, and eclampsia. Posterior reversible encephalopathy syndrome (PRES) An illness in which a person can present with acutely altered mentation, drowsiness or sometimes stupor, visual impairment (e.g., visual hallucinations, cortical blindness, hemianopia, quadrantanopia, and diplopia), seizures (focal or general tonic-clonic), and sudden or constant, non-localized headaches.   Symptoms appear when the blood glucose has descended to about 30 mg/dL, nervousness, hunger, flushed facies, sweating, headache, Hypoglycemic palpitation, trembling, and encephalopathy anxiety.  These gradually give way to confusion and drowsiness or occasionally, to excitement, overactivity, and bizarre or combative behavior.   Blood glucose levels of approximately 10 mg/dL are associated with deep coma, dilatation of pupils, pale Hypoglycemic skin, shallow respiration, encephalopathy slow pulse, and hypotonia, what had in the past been termed the “medullary phase” of hypoglycemia. Common causes of hypoglycemic encephalopathy Depletion of liver glycogen, which Accidental or occasionally follows deliberate Islet cell insulin- a prolonged overdose of insulin secreting tumor of or an oral diabetic the pancreas alcoholic binge, agent starvation, or any form of severe liver failure  Uremia is a clinical condition associated with declining renal function and is characterized by fluid overload, electrolyte imbalances, metabolic abnormalities, and physiological changes. Uremic encephalopathy Urea exhibits direct and indirect toxicity to various tissues, notably affecting the neurological system. Urea acts as a marker for uremic toxins in general, with over 100 substances identified as potential uremic toxins, which are present in varying concentrations in the blood.  Apathy, fatigue, inattentiveness, and irritability are usually the initial symptoms; later, there is confusion, dysarthria, tremor, and asterixis. Uremic Infrequently, this takes the form of a encephalopathy toxic psychosis, with hallucinations, delusions, insomnia, or catatonia As the uremia worsens, the patient lapses into a quiet coma. Unless the accompanying metabolic acidosis is corrected, Kussmaul breathing appears and gives way to Cheyne-Stokes breathing and death.  Apathy, fatigue, inattentiveness, and irritability are usually the initial symptoms; later, there is confusion, dysarthria, tremor, and asterixis. Uremic Infrequently, this takes the form of a encephalopathy toxic psychosis, with hallucinations, delusions, insomnia, or catatonia As the uremia worsens, the patient lapses into a quiet coma. Unless the accompanying metabolic acidosis is corrected, Kussmaul breathing appears and gives way to Cheyne-Stokes breathing and death. Cranial nerve palsies  OLFACTORY NERVE (CN I): PROVIDING THE SENSE OF SMELL. OPTIC NERVE (CN II): PROVIDING VISION. OCULOMOTOR NERVE (CN III): OPENING AND MOVING YOUR EYES AND ADJUSTING PUPIL WIDTH. TROCHLEAR NERVE (CN IV): LOOKING DOWN AND MOVING YOUR EYES TOWARD YOUR NOSE OR AWAY FROM IT. TRIGEMINAL NERVE (CN V): PROVIDING SENSATIONS IN YOUR EYES, MOST OF YOUR FACE AND INSIDE YOUR MOUTH. IT ALSO ALLOWS YOU TO CHEW FOOD. There are 12 ABDUCENS NERVE (CN VI): MOVING YOUR EYES FROM LEFT TO RIGHT. Cranial nerves FACIAL NERVE (CN VII): CONTROLLING SEVERAL FACIAL MUSCLES TO MAKE FACIAL EXPRESSIONS AND PROVIDING THE SENSE OF TASTE IN PART OF YOUR TONGUE. but only some VESTIBULOCOCHLEAR NERVE (CN VIII): PROVIDING THE SENSE OF HEARING of them control AND BALANCE. GLOSSOPHARYNGEAL NERVE (CN IX): PROVIDING TASTE SENSATIONS TO motor function PART OF YOUR TONGUE AND CONTROLLING MUSCLES FOR SWALLOWING. IT ALSO HAS PARASYMPATHETIC NERVE FIBERS THAT PLAY A ROLE IN BLOOD PRESSURE REGULATION AND SALIVA (SPIT) PRODUCTION. VAGUS NERVE (CN X): REGULATING SEVERAL AUTOMATIC BODILY PROCESSES, INCLUDING YOUR DIGESTION, BLOOD PRESSURE, HEART RATE, BREATHING, MOOD, SALIVA PRODUCTION AND MORE. IT’S THE MAIN NERVE OF YOUR PARASYMPATHETIC NERVOUS SYSTEM. ACCESSORY NERVE OR SPINAL ACCESSORY NERVE (CN XI): CONTROLLING SHOULDER AND NECK MOVEMENT. HYPOGLOSSAL NERVE (CN XII): CONTROLLING TONGUE MOVEMENT, WHICH PLAYS A ROLE IN SPEAKING, EATING AND SWALLOWING. A ROLE IN SPEAKING, EATING AND SWALLOWING. CN III: Occulomotor nerve  The somatic efferent portion of the nerve innervates the levator palpebrae superioris muscle; the superior, medial, and inferior rectus muscles; and the inferior oblique muscle.  The visceral efferent portion innervates two smooth intraocular muscles: the ciliary and the constrictor pupillae. CN III: Occulomotor nerve In a complete third nerve palsy, there is ptosis with a divergent and slightly depressed eye. Extraocular movements are restricted in all directions except laterally (preserved lateral rectus function) CN III: Occulomotor nerve Pupillary involvement, manifesting as a relatively dilated pupil that does not constrict normally to light Causes of isolated third nerve palsy without pupillary involvement include diabetes mellitus, hypertension, giant cell arteritis, and herpes zoster. CN IV: Trochlear nerve  The trochlear nerve innervates the superior oblique muscle.  is the only crossed cranial nerve. It originates from the trochlear nucleus, crosses within the midbrain, and then emerges contralaterally on the dorsal surface of the brain stem.  The trochlear nerve enters the orbit via the superior orbital fissure from where it innervates the superior oblique muscle CN IV: Trochlear nerve  Fourth nerve palsy causes upward deviation of the eye with failure of depression on adduction. In acquired cases, there is vertical and torsional diplopia that is most apparent on looking down. CN IV: Trochlear nerve  For superior oblique palsies, the patient tilts the head away from the side of the palsy, and the diplopia worsens with downgaze away from the side of the affected eye  In Brown’s syndrome, the superior oblique is restricted in the trochlea, causing inability to elevate the eye in adduction CN VI: Abducens nerve  The abducens nerve arises from neurons of the abducens nucleus , emerges from the pontomedullary fissure, passes through the cavernous sinus close to the internal carotid, and exits from the cranial cavity via the superior orbital fissure.  Its long intracranial course makes it vulnerable to pathologic processes in the posterior and middle cranial fossae.  The nerve innervates the lateral rectus muscle CN VI: Abducens nerve  Sixth nerve palsy causes convergent squint in the primary position with failure of abduction of the affected eye, producing horizontal diplopia that increases on gaze to the affected side and on looking into the distance  It is an important sign of raised intracranial pressure and may also be due to trauma, neoplasms, brainstem lesions, petrous apex lesions, or medical causes (such as diabetes mellitus, hypertension, giant cell arteritis, and herpes zoster). Management of cranial nerve palsies  In recent-onset isolated  All patients with recent- third nerve palsy, especially onset double vision should if there is pupillary be referred urgently to a involvement or pain, neurologist or immediate referral is ophthalmologist, required for neurologic assessment and possibly particularly if there are CT, MRI, or catheter multiple cranial nerve angiography for intracranial dysfunctions or other aneurysm. neurologic abnormalities. Case  A 56-year-old white male with a history of The most likely diagnosis is hypertension and diabetes complains of double which of the following? vision and pain for the past 2 days. On examination, his vision is OD 20/50 and OS 20/25. He has a larger pupil with a RAPD OD. A. First nerve palsy  The lid of his right eye is slightly lower than the left. His right eye is deviated slightly temporally B. Fourth nerve palsy and inferiorly, and he has difficulty adducting and elevating the eye. C. Third nerve palsy  The most likely diagnosis is which of the following? D. Sixth nerve palsy The end