Asaf Honig

Total and Proteinase K-Resistant α-Synuclein Levels in Erythrocytes, Determined by their Ability to Bind Phospholipids, Associate with Parkinson’s Disease

A marker for diagnosis of Parkinson’s disease (PD), which reflects on the occurrence of peripheral pathogenic mechanisms, would potentially improve therapy. The significance of α-Synuclein (α-Syn) expression in red blood cells (RBC) is currently unclear. Here we investigated whether RBC’s-expressed α-Syn may associate with PD. To this aim, we determined the levels of total and proteinase K-resistant α-Syn in samples of packed red blood cells (PRBCs). Twenty-one individuals with PD at various disease stages and 15 healthy controls, with similar demographic features, were recruited to this study. α-Syn levels were determined by their biochemical property to bind phospholipids, using a phospholipid-ELISA assay. A significantly lower ratio of total-to-proteinase K-resistant α-Syn levels was detected in PD patients than in the healthy control group. However, there was considerable overlap between the two groups. Suggesting a need for additional markers to be tested in combination with α-Syn levels. To the best of our knowledge, this is the first evidence for an association between RBCs-expressed α-Syn and pathogenic mechanisms involved in PD.

Acute bithalamic infarct manifesting as sleep-like coma: A diagnostic challenge.

Bilateral thalamic infarction (BTI) typically presents as a sleep-like coma (SLC) without localizing signs, posing a diagnostic challenge that may lead the treating physician to search for toxic or metabolic causes and delay treatment. We review our experience with BTI of different etiologies, and emphasize the critical role of timely imaging, diagnosis, and management in a series of 12 patients with a presentation of SLC and acute BTI who were managed in our Medical Centers from 2006-2015. In 11/12, urgent head CT scans showed normal brain tissue, while diffusion-weighted (DWI) MRI revealed symmetric bilateral thalamic hyperintense lesions with variable degrees of brainstem involvement. In 1/12, CT scans revealed a contralateral subacute stroke from a thalamic infarct 1month earlier with a unilateral hyperintense lesion on DWI-MRI. From clinical and imaging findings (DWI-MRI, CT angiography and venography), etiology was attributed to embolic causes (cardio-embolism, artery-to-artery mechanism), small vessel disease, or deep sinus vein thrombosis secondary to dural arteriovenous (AV) fistula. Three patients had good outcomes after prompt diagnosis and optimal treatment in <3hours (intravenous tissue plasminogen activator in two patients cardio-embolic etiology and neuro-endovascular repair in one patient with venous infarction due to a dural AV fistula). The diagnosis was made beyond the therapeutic window in seven patients, who were left with significant neurological sequelae. Higher awareness of BTI presenting as SLC is warranted. Optimal patient management includes urgent DWI-MRI. In cases of BTI, further imaging workup is indicated to provide a comprehensive assessment for etiology. Early diagnosis and prompt, targeted intervention are crucial.

Sandfly virus seroconversion associated with neurologic presentation

Objective: To describe the clinical presentation and unique neurologic manifestations of sandfly viruses (SFVs) in the Jerusalem area. Methods: We identified all patients with acute seroconversion to SFV at the Hadassah-Hebrew University Medical Centers during the years 2008–2013 and retrospectively collected and analyzed the clinical and imaging data. Results: Nine patients (ranging from 1.5 to 85 years old) were identified. Presentation included acute neurologic disease, mostly with fever, change in consciousness and behavior, seizures, headache, meningitis, limb paresis, or myelitis. Eight patients had clinical signs of meningitis, meningoencephalitis, or encephalitis alone. Four patients had myelitis. MRI identified pathologic symmetrical changes in the basal ganglia, thalami, and other deep structures in 5 patients, and additional myelitis of the spine was noted on imaging in 3 patients. Seven patients had long-term follow-up: 4 completely recovered and 3 had remaining neurologic sequelae, among them 1 with permanent severe brain damage. Conclusion: Neurologic involvement associated with acute SFV infections is considered to be benign. However, in this series, all 9 patients presented with significant neurologic pathology associated with a unique finding of myelitis and symmetrical basal ganglia, thalami, or white matter involvement. Thus, acute SFV infection should be included in the differential diagnosis in febrile onset of neurologic manifestations and neuroradiologic changes.

Iatrogenic intracranial hypotension and cerebral venous thrombosis.

OBJECTIVE To assess the manifestations of cerebral venous thrombosis (CVT) associated with intracranial hypotension (IH) following lumbar puncture (LP) or spinal anesthesia (SA). METHODS Adult patients with acute CVT unrelated to infection, neurosurgery, or otolaryngological surgery were identified. CVT manifesting within 21days after LP/SA was considered associated with iatrogenic IH. Presentation of patients with and without associate IH was compared. RESULTS 42 patients were included. 11/42 who had undergone LP/SA presented symptoms and imaging characteristics of IH; 31 had no evidence of IH. Those with IH were more often females (11/11 vs. 21/31, p=0.03), presented sooner after symptom onset (6.0±2.2 vs. 15.6±14days, p=0.002), and rates of venous infarction (45% vs. 23%) and seizures (27% vs. 10%) appeared somewhat elevated (p<0.15). Patients with CVT associated with IH had significantly more cortical vein thrombi (55% vs. 16%, p=0.02). Thrombi were significantly shorter in patients with IH (102±113mm vs. 246±133mm, p=0.002). CONCLUSION Patients with CVT secondary to IH were typically younger females, and presented with a more acute and severe course with frequent venous infarcts. Although thrombi in the IH group were less extensive, they were more often symptomatic.

Drops in Barometric Pressure Are Associated with Deep Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE The objective of this study is to assess the effects of changes in barometric pressure and outdoor temperature on the incidence of different subtypes of intracerebral hemorrhage (ICH). METHODS Consecutive patients with primary supratentorial ICH were included. All patients resided in the same geographic area. We compared patients with subcortical ICH to those with cortical ICH. Meteorological data were continuously accrued. High-risk ICH days were defined as those on which 1 or more patients with ICH were admitted and compared to non-high-risk days. We analyzed the relationship between spontaneous ICH location and averaged daily atmospheric pressures and temperatures. RESULTS We included 206 patients (147 with deep ICH and 59 with lobar ICH). Patients with deep ICH were younger (P < .001), more often had histories of diabetes, smoking and previous lacunar strokes, and were more often male (P < .01 for all). Drops in mean air pressure 2 days prior to the ictus were associated with deep but not lobar ICH (P = .006). Deep ICH clustered during February months in parallel with larger changes in barometric pressures (P < .001). CONCLUSIONS Drops in daily atmospheric pressures were associated with deep but not cortical ICH, suggesting a link to hypertensive etiology. Changes in barometric pressures were also associated with higher monthly frequencies of ICH.

Effects of Valproic Acid on Cerebral Nutrient Carriers' Expression in the Rat

Objective: The antiepileptic drug valproate has been shown to affect the expression of carriers for essential compounds and drugs in extracerebral tissues. The aim of the current study was to evaluate in vivo the effect of valproate treatment on the cerebral expression of carriers and selected genes of the blood-brain barrier (BBB) in the rat. Methods: Male Wistar rats were treated daily for 7 days by intraperitoneal injections of valproate (75, 150, or 300 mg/kg/day) or the vehicle. mRNA was isolated from the cerebral cortex and the hippocampus. Transcript levels of 37 genes were measured using a customized gene expression assay. Quantitative histone acetylation was evaluated by western blotting. Glucose6-phosphate (G6P) tissue levels were used as a surrogate of cerebral glucose concentrations. Results: Valproate treatment was associated with significant reduction (up to 22%; P < 0.05) in cortical and hippocampal claudin 5-normalized Slc2a1 (Glut1) mRNA expression. G6P levels were not significantly altered, but were correlated with Slc2a1 transcript levels (r = 0.499; P < 0.02). None of the other 36 screened genes were significantly affected by valproate. Cortical histone hyperacetylation indicated cerebral activity of valproate on a major pathway regulating gene expression (P < 0.02). Significance: The effect of valproate on nutrient carriers appears to be tissue-specific and even brain area-specific. If validated in humans, the changes in Glut1 expression might have clinical implications in positron emission tomography (PET) imaging. Further studies are required for elucidating the relevance of these findings to the clinic.

Confined anterior cerebral artery infarction manifesting as isolated unilateral axial weakness

We describe isolated unilateral axial weakness in three patients eventually diagnosed with anterior cerebral artery infarction (ACAI), a new clinical observation. Files of three ACAI patients (2 females, 1 male, ages 55-80) were retrospectively reviewed. All three presented to the ED with sudden unsteadiness. On initial neurological examination, all three patients manifested unilateral truncal deviation to the side contralateral to the weakness, even while seated. There was significant unilateral hypotonia due to substantial paravertebral weakness. None had pyramidal signs or increased limb tone. Speech, language, and cognitive performance were intact during admission examination. In all three patients, initial diffusion-weighted imaging (DWI) MRI showed small confined regions of restriction involving the posterolateral border of ACA territory; CT angiography was normal in one patient with a newly diagnosed atrial fibrillation but showed atherosclerotic vasculature with severe narrowing of the A3 segment of the ACA in two. Awareness of ACAI presenting as unilateral axial weakness is warranted. We suggest that optimal diagnostic management should include examination of axial tone. Ischemic involvement of distal ACA branches may herald a more extensive ACAI. Prompt diagnosis may enable thrombolysis or endovascular treatment, and blood pressure maintenance may allow adequate perfusion to damaged tissue.

Asystole in the epilepsy unit

BackgroundEarly identification of cardiac asystole as a reason for syncope is of uttermost significance, as insertion of a cardiac pacemaker can save the patient’s life and prevent severe injury. The aim of this work was to emphasize the subtle and unusual presentations of asystole in patients evaluated in epilepsy units.MethodsWe reviewed the clinical presentation, ECG and EEG data of a series of seven patients who were evaluated in four epilepsy units and were diagnosed with asystole.ResultsThree patients had unusual clinical manifestations of cardiac asystole, resembling epileptic seizures. Three patients had asystole induced by epileptic seizures and in one patient the diagnosis was not clear. All patients except one were implanted with a pacemaker and improved clinically.ConclusionsSeizure-induced asystole is a rare complication of epilepsy and asystole may clinically mimic epileptic seizures. A high level of suspicion and thorough prolonged cardiac and EEG monitoring are mandatory for reaching the right diagnosis. As the diagnosis is rare and difficult to reach, a flow chart to assist diagnosis is suggested.

Spinal ischemic stroke following dialysis: clinical and radiologic findings

Spinal cord ischemia (SCI) is a relatively common cause of noncompressive myelopathy.1 SCI frequently involves the thoracic or lumbar cord manifesting as acute painful paraparesis but may also involve the posterior columns and autonomic fibers.2 Most infarcts affect the central parts of the anterior spinal artery supply.2–4 Outcome depends on the initial severity of the neurologic deficits and may be surprisingly benign especially if proprioception remains intact.1,2 Because hypoperfusion may cause SCI,5,6 our goal was to describe SCI as a potential complication of hemodialysis-associated hypoperfusion.