Worthy Warnack

Effects of chronic desipramine treatment on rat brain noradrenergic responses to α-adrenergic drugs☆

It has been previously reported that long-term tricyclic antidepressant treatment in the rat causes a subsensitivity of central beta-receptor-stimulated adenylate cyclase along with alterations of brain norepinephrine (NE) content and metabolism. We have confirmed earlier findings that after one week of desipramine treatment (5.0 mg/kg b.i.d.) brain NE levels decline while NE metabolism is similar to control animals, but is above control after 12 days of treatment. Single cell recordings from noradrenergic neurons of the locus coeruleus (LC) show that after one week of desipramine treatment, neuronal firing rate is lower than in control rats but greater than that seen in response to acutely administered drug. Furthermore, desipramine injection in a dose which profoundly altered LC impulse flow in control rats produced little or no effect on impulse flow in chronically treated rats. Of 25 or 250 microgram/kg doses of clonidine, which are equieffective for decreasing brain NE metabolism in control animals, only the larger dose decreased NE metabolism in 12 day desipramine-treated rats. The postsynaptic alpha-antagonist prazosin (5.0 mg/kg) increased NE metabolism in both groups. These results suggest that presynaptic (alpha 2) adrenoreceptors become subsensitive during long-term desipramine treatment, thus allowing recovery of noradrenergic impulse flow in the presence of NE uptake inhibition.

Herpes Simplex Encephalitis as a Potential Cause of Anti-N-Methyl-D-Aspartate Receptor Antibody Encephalitis Report of 2 Cases

IMPORTANCE Encephalitis mediated by anti-N-methyl-D-aspartate (NMDA) receptor antibodies and herpes simplex (HS) encephalitis are seemingly separate causes of encephalopathy in adults and children. Herpes simplex encephalitis is infectious, and anti-NMDA receptor antibody encephalitis is autoimmune in origin. Both can cause seizures and encephalopathy, although the latter can also cause psychiatric symptoms and movement disorders. Owing to the rarity of these 2 diseases, patients with co-occurrence are important because they alert clinicians to possible links between 2 seemingly separate processes. OBSERVATIONS In a case series of 2 patients observed at our center, we describe an infant and an adult who had confirmed HS encephalitis and then developed confirmed anti-NMDA receptor antibody encephalitis. Polymerase chain reaction testing for HS virus was performed. Testing for NMDA receptor antibodies was performed by Associated Regional and University Pathologists Laboratory in Salt Lake City, Utah. CONCLUSIONS AND RELEVANCE We conclude that atypical cases of HS or other viral encephalitides should be investigated for concomitance of an autoimmune encephalitis. We suspect that the pathophysiologic mechanisms by which HS virus infects neurons produce a higher likelihood of contracting anti-NMDA receptor antibody encephalitis.

The spectrum of autoimmune encephalopathies

Despite being a potentially reversible neurological condition, no clear guidelines for diagnosis or management of autoimmune encephalitis exist. In this study we analyzed clinical presentation, laboratory and imaging characteristics, and outcome of autoimmune encephalitis from three teaching hospitals. Non-paraneoplastic autoimmune encephalitis associated with antibodies against membrane antigens was the most common syndrome, especially in the pediatric population. Clinical outcome was better for patients with shorter latency from symptom onset to diagnosis and initiation of immunomodulation. Patients with underlying malignancy were less likely to respond well to immunomodulatory therapy. The clinical spectrum of autoimmune encephalitis is fairly broad, but prompt recognition and treatment often leads to excellent outcome.

Factors contributing to delay in diagnosis of Guillain‐Barré syndrome and impact on clinical outcome

Heterogeneity of presenting symptoms makes the initial clinical diagnosis of Guillain‐Barré syndrome (GBS) challenging.

Multifocal paraneoplastic cortical encephalitis associated with myasthenia gravis and thymoma

OBJECTIVES To report a case of multifocal cortical encephalitis associated with thymoma and to establish an association of this thymoma-related paraneoplastic syndrome with voltage-gated potassium channel antibodies. DESIGN Case report. SETTING University hospital. PATIENT A 43-year-old woman with a history of seropositive myasthenia gravis and successfully treated invasive thymoma. Four years after thymectomy, she presented with seizure and rapidly progressive confusion and aphasia. Myasthenia gravis remained in pharmacological remission. Magnetic resonance imaging of the brain showed innumerable cortically based signal abnormalities as well as extensive left mesial temporal lobe abnormality with minimal enhancement. RESULTS Chest computed tomography showed abnormal pleural thickening of the left lung, which proved to be recurrent metastatic thymoma. Results of serological evaluation were positive for acetylcholine receptor, striational, and voltage-gated potassium channel antibodies. She showed partial improvement in response to immunotherapy and chemotherapy but ultimately died 2 months later of tumor complications. CONCLUSIONS Thymoma and myasthenia gravis may be associated with other autoimmune neurological disorders including paraneoplastic encephalitis. This second case of thymoma-associated multifocal cortical encephalitis demonstrates that autoimmune encephalitis can extend to cortical regions outside the limbic system. Autoimmune encephalitis should be considered in the differential diagnosis of patients with myasthenia gravis or thymoma who develop new cognitive symptoms.

Clinical Reasoning: A 41-year-old comatose man with absent brainstem reflexes

A 41-year-old obese man was stopped by the police for driving erratically. He was confused, dysarthric, ataxic, and vomited repeatedly before collapsing and becoming rapidly obtunded, eventually requiring rapid sequence intubation (RSI). He arrived at the emergency department (ED) with a Glasgow Coma Scale score of 3, hypothermia (35.3°C), and hypotension (78/38 mm Hg), with a heart rate of 80. He was treated with warm IV fluid boluses and warming blanket. He was examined by the attending and resident neurologists approximately 2.5 hours from the time of RSI. He was mechanically ventilated but had received no sedation since intubation. Nothing was known about his medical history and no collateral information was available. He did not respond to naloxone or thiamine. Clinical examination was performed with a temperature of 36°C and a blood pressure of 120/80 mm Hg. He remained mechanically ventilated without spontaneous respirations. No meningismus, external signs of trauma, needle puncture marks, or tongue or buccal lacerations were observed. Spontaneous movements were absent. He did not open his eyes, grimace, withdraw, or posture to noxious stimuli (nailbed and supraorbital pressure). Neuromuscular blockade was excluded with a train of 4 twitches with maximal ulnar nerve stimulation. His pupils were fixed at 2 mm and unreactive to light. Corneal and oculocephalic (vertical and horizontal) reflexes were absent. Irrigation of each ear canal with ice water produced no eye deviation. No gag or cough reflexes were elicited with posterior pharyngeal stimulation and tracheal suctioning respectively. His extremities were flaccid and areflexic. Babinski sign was absent. No gaze deviation, nystagmoid eye movements, facial twitching, or jerking movements were observed. Cardiovascular, lung, and abdominal examinations were unremarkable. ### Questions for consideration: 1. How do you approach a comatose patient? 2. What are the differential diagnoses? GO TO SECTION 2 The comatose patient who presents to the ED is a challenge. …

Optic neuritis presenting with amaurosis fugax

Optic neuritis usually presents with rapid and gradual loss of vision that is either complete or incomplete, and typically associated with retro-orbital pain. To our knowledge there have been no documented reports of optic neuritis presenting with multiple episodes of amaurosis fugax, the sudden and transient loss of vision lasting seconds to minutes. We report here the case of a young woman with a possible diagnosis of demyelinating left optic neuritis that presented solely with multiple episodes of brief and transient sudden loss of vision. Ophthalmological exams were normal between episodes of vision loss. The patient’s magnetic resonance imaging of the brain showed a subtle enhancement of the left optic nerve along with multiple periventricular lesions, highly suggestive of a demyelinating disease. The frequent episodes of visual loss resolved completely with high dose parenteral steroids. Neurologists and other clinicians should be aware of this unusual presentation of optic neuritis as treatment modalities differ greatly from other causes of amaurosis fugax.

Novel use of levodopa in human immunodeficiency virus encephalopathy-mediated parkinsonism in an adult

We report a case of a 36-year-old man with a medical history of human immunodeficiency virus (HIV) infection who presented with hypomimia, hypophonia, bradykinesia, rigidity, and freezing of gait. His clinical presentation and magnetic resonance imaging were consistent with HIV encephalopathy with involvement of the bilateral basal ganglia and diffuse leukoencephalopathy. We initiated a trial of carbidopa-levodopa. The dose was escalated to 1050 mg levodopa daily. Amantadine was also started. The patient was closely monitored for behavioral, neurological, or systemic side effects. He tolerated therapy well without adverse effects. The patients neurological status significantly improved with levodopa, including hypomimia, hypophonia, bradykinesia, and fluidity of gait. This case demonstrates that carbidopa-levodopa can be safely utilized to manage parkinsonism in an adult patient with HIV encephalopathy.

Clinical Reasoning: A woman with recurrent aphasia and visual field defects

A 73-year-old woman with a history of hypertension and a recent stroke presented with recurrent nonsensical speech and visual problems. One month prior, she had been diagnosed with a stroke after sudden-onset speech and visual difficulties that resolved after a few hours. Thirteen days before, she had had a second episode of similar symptoms. She was seen in our institution after a few hours of sudden-onset unintelligible speech. Her vital signs were within normal limits. She was not in distress but appeared frustrated. Her general physical examination was unremarkable. She had no carotid, ophthalmic, or cranial bruits. Her neurologic examination was notable for fluent aphasia with paraphasic errors and inability to name, read, or write. She also had right homonymous hemianopia, right-sided sensory loss, and generalized brisk deep tendon reflexes. The rest of her neurologic examination showed no abnormalities.

Carotid Cavernous Fistula Imitating Brainstem Glioma

A 45-YEAR OLD WOMAN who had an injury from a motor vehicle crash 9 months prior to being admitted to the hospital reported experiencing 3 months of nausea and vomiting, progressive dysphagia to solids and liquids, and a 15-pound weight loss. The motor vehicle crash had resulted in skull fractures and a subarachnoid hemorrhage. On examination, she was found to be dysarthric with monotonal hypophonia and mild leftarm ataxia. Because she had an elevated creatinine level, noncontrasted magnetic resonance imaging of the brain was performed. The results showed an increased fluidattenuated inversion recovery signal within thepontomedullary regionand the left cerebellar hemisphere (Figure, A-C). Because of this finding, together with the woman’s weight loss and progressive clinical course, there was concern for a neoplastic process. However, the results of magnetic resonance spectroscopy indicated brainstem edema, and the results of noncontrasted magnetic resonance imaging of the cervical spine suggested a vascular malformation (Figure, D). To further evaluate the vascular malformation, a cerebral angiogram was performed, the results of which demonstrated a direct carotid cavernous fistula (CCF) as a rare cause of the brainstem edema (Figure, E). Ten days after endovascular coiling of the CCF, the patient regained her ability to swallow and was discharged from the hospital. At home, she tolerated a regular diet and was ambulatory and selfsufficient.