Zeev Nitsan

Plasma homocysteine levels and parkinson disease : Disease progression, carotid intima-media thickness and neuropsychiatric complications

Objective: To determine whether plasma homocysteine (Hcy) levels are associated with clinical characteristics, neuropsychological and psychiatric manifestations and cardiovascular comorbidity in patients with Parkinson disease (PD). Background: Elevated Hcy levels are linked to atherosclerosis, vascular disease, depression, and dementia. Patients with PD treated with L-dopa have been shown to have elevated Hcy levels. Design/Methods: Idiopathic PD patients were evaluated using the Unified Parkinsons Disease Rating Scale, Hoehn and Yahr stage, Parkinson Psychosis Rating Scale, Beck Depression Inventory, Frontal Assessment Battery, Mini-Mental Status Examination, and several tests for frontal type cognitive functions. Fasting blood samples were collected for the measurement of Hcy, and carotid B-mode ultrasound was performed to measure intima-media thickness of the common carotid arteries. Results: Seventy-two consecutive PD patients (46 men; average age, 68.7 ± 11.6 years; average disease duration, 7.0 ± 4.7 years) were recruited. All but 10 patients were treated with L-dopa. The average level of Hcy was 16.4 ± 7.8 &mgr;mol/L, and 38.9% of the patients had Hcy level above the reference range (>15.0 &mgr;mol/L). The Hcy levels were associated with PD duration as they were with L-dopa treatment duration but were not associated with the parameters of disease severity or with L-dopa dose. The Hcy levels were associated neither with the common carotid intima-media thickness nor with cardiovascular morbidity. No association was found between Hcy and the neuropsychiatric features of PD such as depression, cognitive performance, or psychosis. Conclusions: Hyperhomocystinemia is common in L-dopa-treatedPD patients but was not associated with neuropsychological complications (depression, dementia, and cognitive decline associated with frontal lobe functioning or psychosis), enhanced disease severity, or vascular comorbidity.

The Frontal Assessment Battery as a Tool for Evaluation of Frontal Lobe Dysfunction in Patients With Parkinson Disease

Background: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests. Objectives: To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD. Methods: Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman’s r. Results: Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05). Conclusions: In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.

CSF tau correlates with CJD disease severity and cognitive decline

Creutzfeldt–Jakob disease (CJD) is the most common prion disease in humans. The clinical diagnosis of CJD is supported by a combination of electroencephalogram, MRI, and the presence in the CSF of biomarkers. CSF tau is a marker for neuronal damage and tangle pathology, and is correlated with cognitive status in Alzheimers disease (AD).

Pruritus in familial Creutzfeldt–Jakob disease: a common symptom associated with central nervous system pathology

Pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with Creutzfeldt–Jakob disease (CJD), and its anatomical background is not well defined. The present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in CJD patients and investigate its anatomical substrate by MRI. The study group included consecutive familial and sporadic CJD patients carrying the E200K PRNP mutation followed up in a longitudinal prospective study between the years 2005 and 2008. Pruritus was prospectively screened for and diffusion-weighted imaging (DWI) was used to correlate brain diffusion abnormalities with pruritus in CJD patients. Pruritus was present in 6/31 (19.35%) patients with familial disease (fCJD) and in none of the patients with sporadic disease (sCJD). Pruritus was a presenting symptom in one patient and evolved during the course of the disease in the other five patients. The pruritus was generalized in three patients, regional in two and localized in one patient. It was transient in one patient and continued throughout the disease in five patients. DWI showed that pruritus was significantly associated with reduced diffusion in the several areas known to be affected by CJD, but most significantly in the midbrain periaqueductal grey matter. Pruritus is relatively common in patients with familial CJD carrying the E200K mutation. Our findings point to a central origin that involves damage to the inhibitory gating mechanism for itch in the periaqueductal grey matter.

Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

Familial Creutzfeldt−Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke‐like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD.

Repetitive deep transcranial magnetic stimulation for motor symptoms in Parkinson's disease: A feasibility study

OBJECTIVES Repetitive transcranial magnetic stimulation (rTMS), using standard coils, provided modest symptomatic benefits in patients with Parkinsons disease (PD). In our previous exploratory studies, using the newly developed Hesed coil (providing deeper rTMS; rDTMS) high frequency (HF), excitatory rDTMS over the primary motor cortex (M1), did not achieve sufficient beneficial effect for PD symptoms, while low frequency (LF) inhibitory stimulation, was mildly beneficial. To further investigate the optimal rDTMS stimulation parameters for PD patients, and to assess whether there is an added value for dual stimulation, consisting of HF rDTMS over the prefrontal cortex (PFC) along with LF M1 rDTMS. The rational for the selection of the current stimulation parameters and sites lies on the previous studies that demonstrated an inhibitory effect of 1Hz rTMS on the increased cortical activity in PD as well as dopamine release by PFC stimulation. PATIENTS AND METHODS An open comparative active study of one month duration (12 sessions) of LF rDTMS over M1 alone (n=9) or combined with HF PFC rDTMS (M1-PFC, n=10). Outcome measures included the total and motor Unified Parkinsons Disease Rating Scale scores (T-UPDRS and M-UPDRS) and other variables, were collected at baseline and on days 30 and 60. RESULTS For the M1+PFC group, T-UPDRS score improved from baseline to day 30, by 15% (median: 52 points, decreased to 44, p=0.02, effect size: 0.51) and M-UPDRS score improved by 24% (median: 37 points decreased to 28, p=0.04, effect size: 0.47). The corresponding results for the M1 group were insignificant. Additionally, the between groups comparison, was insignificant. CONCLUSION rDTMS, consisting of M1 excitation with PFC inhibition improved PD motor symptoms but was not significantly superior to M1 rDTMS alone. rDTMS stimulation protocols for M1 should be further evaluated in larger scale controlled studies.

Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease

Although seizures (other than myoclonus) are frequently reported in Creutzfeldt‐Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown.

CSF tau correlates with the degree of cortical involvement in E200K familial Creutzfeldt-Jakob disease

Cerebrospinal fluid (CSF) tau was found to correlate with disease severity and cognitive status in E200K familial Creutzfeldt-Jakob disease (fCJD) patients. The objective of the present study was to test whether tau levels in the CSF also correlate with the disease burden as reflected by the degree of cortical involvement in DWI MRI. Forty-four consecutive E200K fCJD patients (25 males, mean age 58.6±7.5, range 48-75 years) were recruited to the study and had a CSF tau examination as well as measurements of the extent of the cortical involvement in the DWI axial MRI. Correlation was tested using Pearson test. A significant correlation (r=0.617 p<0.0001) was found between CSF tau levels and the extent of cortical involvement. This correlation between tau levels and the disease burden reinforce the notion that tau can be used as a biomarker reflecting the extent of disease in patients with E200K fCJD.

The CJD Neurological Status Scale: A New Tool for Evaluation of Disease Severity and Progression in Creutzfeldt - Jakob disease

Cohen OS, Prohovnik I, Korczyn AD, Ephraty L, Nitsan Z, Tsabari R, Appel S, Rosenmann H, Kahana E, Chapman J. The Creutzfeldt–Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression.
Acta Neurol Scand: 2011: 124: 368–374.
© 2011 John Wiley & Sons A/S.

The Creutzfeldt-Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression: A new neurological scale for the evaluation of Creutzfeldt-Jakob disease

Cohen OS, Prohovnik I, Korczyn AD, Ephraty L, Nitsan Z, Tsabari R, Appel S, Rosenmann H, Kahana E, Chapman J. The Creutzfeldt–Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression.
Acta Neurol Scand: 2011: 124: 368–374.
© 2011 John Wiley & Sons A/S.