Lea Pollak

Symptomatic patients after craniectomy

Various surgical procedures in neurosurgery end with cranial vault defects. It is generally believed that the reason for repair of the skull defect is cosmetic or protective. There is evidence, however, that in selected cases neurologic deterioration can be reversed by cranioplasty. In the sinking scalp flap syndrome the deterioration has been thought to be related to the concavity of the skin flap and underlying brain tissue secondary to atmospheric pressure and also to the in-and-out displacement of the brain through the skull defect. Five cases of symptomatic patients after craniectomy are reported, of which all had a neurologic deterioration that was improved by cranioplasty.

Excessive daytime sleepiness in patients with Parkinson's disease: A polysomnography study

To investigate excessive daytime sleepiness (EDS) in patients with Parkinsons disease (PD), the reasons for which have not yet been clarified, polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT) were performed in 46 patients with PD, and, in addition, PSG was performed in 30 healthy controls. Assessment included Epworth Sleepiness Score (ESS), Mini‐Mental State Examination (MMSE), and Hamilton Test (HT) for depression. Fifty percent of PD patients reported EDS (ESS, 10 ± 4.5 vs. 6.9 ± 3.7; P = 0.01). Compared with controls, PD patients as a group had lower sleep efficiency (65 ± 22 vs. 77 ± 14; P = 0.03), a longer Stage 2 (73 ± 12 vs. 67 ± 12; P = 0.03), and a shorter rapid eye movement stage (8 ± 8 vs. 17 ± 8; P < 0.001). Clinical data and sleep characteristics were similar in PD with/without EDS. Of interest, patients treated with clonazepam (CLNZ) had lower EDS than those without CLNZ (ESS, 7.9 ± 4.7 vs. 11.3 ± 4.0; P = 0.03). These patients suffered less periodic leg movement during sleep (2.1 ± 2.7 vs. 12.4 ± 28; P = 0.04), which might explain the finding. No correlation was found between ESS, MSLT, and all other clinical features analyzed. In PD patients, according to the data obtained, severity of EDS does not depend on any specific clinical factor and the etiology is probably multifactorial. Paradoxically, PD patients treated with CLNZ were less sleepy than patients not treated with CLNZ.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis

Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). Methods: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen–positive slides were analyzed by PCR for VZV DNA. Results: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen–positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen–positive TAs, in 6/10 (60%) VZV antigen–positive skeletal muscles, and in one VZV antigen–positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. Conclusions: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Clozapine in Parkinson's disease psychosis: 5-year follow-up review

The objective of this study was to monitor the long-term effect of clozapine administered to Parkinsons disease (PD) patients with psychosis. Confusion, visual hallucinations, and psychosis are major dose-limiting factors for long-term dopaminergic management of PD. Classic neuroleptic agents exacerbate the motor symptoms of the disease. For this reason, the introduction of atypical antipsychotic drugs has been a major advancement for the management of psychosis in patients with PD. Of them, clozapine is one of the most effective. Thirty-two patients (mean age, 73 years; mean disease duration, 12.2 years) with PD and psychosis (DSM-IV), 14 of them with dementia (DSM-IV), were followed for 5 years with periodic clinical evaluation, Mini Mental State Examination (MMSE), and Parkinsonian Psychosis Rating Scale (PPRS) administered before and following the study (at least once in 6 months). Periodic blood count was performed for tracking neutropenia. Nineteen patients (8 with dementia) have continued to receive clozapine (mean daily dose, 50 mg). Thirteen patients stopped medication: 9 because symptoms improved and did not return after weaning off clozapine; 3 patients because of somnolence; and 1 because of personal reasons. The average duration of treatment in those in whom medication was stopped was 8.5 months (range, 1–24 months). No correlation was found between age, sex, duration, and severity of disease (Yahr scoring), the presence of dementia, and the response to clozapine. Also, the PPRS scoring did not influence clozapine response. No case of neutropenia was found. According to the experience accumulated and the results of the present study, the authors believe clozapine is the best therapeutic choice currently available for the management of psychosis in patients with PD.

Neurological features of West Nile Virus infection during the 2000 outbreak in a regional hospital in Israel

During the summer of 2000, 35 patients with West Nile Virus Fever were admitted to our hospital. Of these, the 26 (21 adults, mean age 56 (19-86) and 5 children (aged 9-15)) presented have neurological involvement, 33% with meningitis, 52% with meningoencephalitis, 10% with encephalitis and 5% with acute polyneuropathy. Presenting clinical features were fever in 95% of cases, headache in 90%, nausea/vomiting in 52%, confusion in 48%, somnolence in 38%, neck stiffness in 33%, a skin rash in 19%, diarrhea in 14%, cervical pain in 14%, seizure in 9%, photophobia in 9% and limb weakness in 4%. Leucopenia was not found. Two patients diagnosed with meningoencephalitis died. Three patients had signs of an acute polyneuropathy, this being the only complaint of one patient. The EEG was abnormal in all cases of meningitis or meningoencephalitis, except in three cases. Outbreaks of West Nile Virus Fever are emerging as a worldwide disease with high rates of neurological involvement and death. It should be considered in cases presenting with aseptic meningoencephalitis, meningitis and acute polyneuropathy, especially during the summer months and in areas along bird migration pathways.

Anxiety in the First Attack of Vertigo

BACKGROUND Although psychiatric disturbances have been reported in chronic vestibular disorders, little is known about the psychological impact of an acute vertigo attack. METHODS We conducted a comparative questionnaire study in 30 patients with a first attack of vestibular dysfunction and in 35 patients with a nonvestibular neurologic deficit of acute onset. RESULTS Patients with vertigo reported more anxiety than patients with nonvestibular neurologic deficits (P = 0.002), despite the fact that premorbid anxiety was similar in both groups (P = 0.5). No difference in anxiety levels was found between vertigo patients who vomited and those who were free of vegetative symptoms (P = 0.97). Vertigo patients felt more disabled than nonvertigo patients (P = 0.06), irrespective of the objective restrictions caused by the disease. The rate of depression did not differ between the groups of patients (P = 0.09). CONCLUSION Patients with acute vertigo experience extreme anxiety, and this contributes to their feeling of disproportionate disability. The reason for emotional disturbances in vestibular dysfunction is probably the result of physiological connections between the vestibular and limbic system and deserves further neuroanatomic investigation.

Comparison of glatiramer acetate (Copaxone®) and interferon β-1b (Betaferon®) in multiple sclerosis patients: an open-label 2-year follow-up

OBJECTIVE To compare the clinical efficacy, as expressed by relapse rate and disability accumulation, and safety profile of glatiramer acetate (Copaxone; COP-1) and Interferon beta-1b (Betaferon; IFN beta - 1b) administered to multiple sclerosis patients during a 2-year follow-up on an open-label parallel design, as compared to their clinical condition in the 2-year period prior to treatment. BACKGROUND Copaxone and IFN beta - 1b have been recently introduced for the treatment of relapsing forms of MS. Both medications have been proven to have a relatively safe profile and are used extensively world-wide. METHODS 58 consecutive patients with relapsing forms of MS were enrolled from the MS out-patient clinic, during three months. After being informed in detail of the two approved treatment options existing at the time in Israel, the patients chose by themselves to receive either: (a) Copaxone 20 mg subcutaneously (sc) daily (Copaxone dly, 20 patients), or (b) Copaxone 20 mg sc alternate-day (Copaxone alt, 18 patients) or (c) IFN beta-1b 8 MIU sc in alternate day (20 patients). Mean relapse rate/year and mean EDSS/year were calculated for each group of patients during the 2 years prior to the onset of treatment, and during the year prior to the onset of treatment. Statistical significance was observed in the relapse rate in the year prior to the onset of treatment between the IFN beta -1b group and the two Copaxone groups (p = 0.05). This statistical difference has no effect on the overall data of the 2 years prior to starting the treatment and on the results. No statistical significance was observed in the total number of relapses, and on the 2-year relapse rate, prior to the onset of treatment. Mean relapse rate/year and mean EDSS/year were calculated for each group during the first and second year of treatment. Wilcoxon analysis for clinical data and chi-square for adverse events were applied. RESULTS The three groups were statistically comparable concerning mean relapse/year in the 2 years before the trial started and no statistical significance was observed among the three groups. A statistically significant reduction in the mean relapse rate in the 2 years after onset of treatment was observed in the three group of patients: Copaxone daily (dly) 1.1 +/- 0.6 (p = 0.0001); Copaxone alternate (alt) 0.9 +/- 0.6 (p = 0.0004) and IFN beta -1b 1.2 +/- 0.7 (p = 0.0001). Disability as expressed by EDSS score prior to the onset of treatment and after 2 years of treatment showed deterioration in the three groups although more significant in the Copaxone groups: Copaxone dly 3.3 +/- 1.4 to 3.8 +/- 1.6 (p = 0.007); Copaxone alt 2.4 +/- 1.1 to 2.8 +/- 1.3 (p=0.04); IFN beta - 1b 3.1 +/- 1.3 to 3.3 +/- 2.0 (N.S.). The most common adverse events reported were: (1) flu-like symptoms 7 pts (35%) in the IFN beta -1b group; 10 pts (26%) of the two Copaxone groups; (2) increased spasticity of lower limbs 3 pts (15%), only in the IFN beta -1b group; (3) site injection reaction (SIR): 16 SIR (80%) in the IFN beta -1b group; 12 SIR (67%) in the Copaxone alt group; 14 SIR (70%) in the Copaxone dly group; and (4) systemic reaction 3 pts (15%) in the IFN beta -1b group; 4 pts (22%) in the Copaxone alt group; 6 pts (30%) in the Copaxone dly group. Premature termination occurred in five patients treated with Copaxone (3 in the alternate group and 2 in the daily group). CONCLUSION The present study, despite the limitations of an open-label study, shows that Copaxone dly, Copaxone alt and IFN beta -1b treatment seem to be equally effective for the control of exacerbations in MS. The adverse event profile, as reported by the patients, was also similar. However, the adverse events profile registered indicated that Copaxone is somewhat less detrimental, whereas disability as measured by EDSS accumulation showed that the interferon beta - 1b patients demonstrated a slower progression of the disability.

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis

IMPORTANCE Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Diagnostic value of vestibular evoked myogenic potentials in cerebellar and lower-brainstem strokes

BACKGROUND Vestibular evoked myogenic potentials (VEMPs) provide assessment of vestibular function. They consist in picking up compound muscle action potentials in the sternocleidomastoid (SCM) muscles in response to auditory stimulation of the vestibulum. VEMP testing has found application mainly in peripheral vestibular disorders, whereas reports about VEMPs in central vestibular lesions are rather scarce. AIMS OF THE STUDY Based on the physiological connections between the cerebellum and the vestibular nuclei, we investigated the influence on VEMPs of cerebellar and lower-brainstem strokes. We examined whether or not this method may be suitable as a clinical tool for the evaluation of the extent of cerebellar strokes. PATIENTS AND METHODS Nineteen patients with cerebellar ischemic stroke and 15 patients with lower-brainstem ischemic stroke (11 in the pons, four in the medulla) were included. The latencies and amplitudes of P13 and N23 in both groups of patients were compared with those obtained in a control group of 53 normal individuals. RESULTS VEMP responses were obtained in all patients and controls. At the group level, mean peak latencies and amplitudes, and the number of subjects with significantly deviant values did not differ between patients and controls. There were no latency or amplitude differences ipsilaterally or contralaterally to the lesion. At the individual level, there was no correlation between laterality of lesion and that of P13 or N23 abnormalities in patients with cerebellar strokes; however, there were two patients (one pontine, one medullar stroke) who presented P13 and N23 latency abnormalities ipsilaterally to the lesion. CONCLUSION Cerebellar strokes do not influence VEMPs. Moreover, despite previous reports, we were unable to find at a group level any statistically significant VEMP changes in patients with lower-brainstem strokes as compared with controls. Therefore, VEMPs do not appear a suitable tool for assessment of brainstem integrity in patients with posterior fossa strokes. However, they could constitute a sensitive method for documentation of involvement of the central vestibular pathways in patients with brainstem stroke.

Vestibulocervical reflexes in idiopathic Parkinson disease.

OBJECTIVES The mechanism of gait instability in Parkinson disease (PD) is not completely understood. We examined the saccular part of the otolith function and its possible contribution to gait difficulties in idiopathic PD. METHODS Fifty-four PD patients (mean age 66 years, 32 men) were included. These were characterized with respect to disease severity, duration, treatment, as well as the presence of disease complications, dementia and depression. Vestibular evoked myogenic potentials (VEMP) were recorded in patients and 53 healthy controls. RESULTS VEMP responses were recorded in all controls. Unilaterally absent VEMP responses were found in 20 (37%) of PD patients and bilaterally absent responses in four (7.4%). All patients with preserved peaks had normal latencies as compared with controls. The number of PD patients with abnormal/absent VEMP was thus significantly higher than in controls (p<0.00). There were no correlations between VEMP abnormality and disease stage, falls or medication. A correlation was found between abnormal VEMP and depression/antidepressant treatment. CONCLUSION PD patients often have absent vestibulocollic reflexes. Further investigations are needed to elucidate the significance of this finding for postural stability and gait in this disorder.