Clinical and neurophysiological aspects of anatomical variants in dorsomedial hand innervation.

OBJECTIVE: Three patients presented with painful paraesthesias in the dorsomedial aspect of the hand after removal of a ganglion cyst of the dorsal lower third of the forearm. This hand territory is usually innervated by the dorsal cutaneous branch of the ulnar nerve (DCU) but here it was innervated by a branch of the radial superficial nerve (RS). Consequently, we aimed to examine the frequency of this variant in the general population. METHODS: Both RS and DCU were stimulated in the forearm and sensory response recorded from the dorsomedial skin area of the hand in the three patients and 100 normal controls. RESULTS: In all three patients, the RS nerve innervated the dorsomedial hand bilaterally. Nineteen out of 100 controls demonstrated variants of dorsomedial skin innervation of the hand on nerve conduction studies: 12 unilaterally and seven bilaterally. Among them, 13 individuals had mixed innervation by both RS and DCU and six by the RS nerve only. CONCLUSION: Nerve conduction studies of both RS and DCU with sensory response recording on the dorsomedial hand area should be considered before surgical procedures on the dorsal lower forearm in order to prevent iatrogenic postoperative sensory nerves lesions.

Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson's disease.

BACKGROUND: The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to levodopa significantly reduces OFF time to the same magnitude as adjunct entacapone. This substudy of LARGO aimed to assess the effect of rasagiline and entacapone on the motor symptoms of PD during the practically defined OFF state. METHODS: LARGO was a randomized, double-blind, multicenter trial that assessed the efficacy and safety of rasagiline (1 mg/day), entacapone (200 mg with each levodopa dose), and placebo in 687 levodopa-treated PD patients with motor fluctuations. A substudy of LARGO measured UPDRS motor scores in the practically defined OFF state in 32 rasagiline, 36 entacapone, and 37 placebo patients. RESULTS: Treatment with rasagiline produced a significant improvement over placebo of 5.64 units in UPDRS motor OFF score (P = 0.013 vs. placebo). By contrast, the effect of adjunct entacapone was not significant (P = 0.14 vs. placebo). Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF score (P = 0.058 vs. placebo), no such trend was noted for entacapone (P = 0.26 vs. placebo). Retrospective analysis, using the Bonferroni correction, of UPDRS motor subdomains further revealed that rasagiline, but not entacapone, significantly improved bradykinesia (P < 0.001) and showed trends for improvements in facial expression, speech, and axial impairment during OFF time. CONCLUSIONS: This study provides the first objectively measured evidence that adjunct rasagiline 1 mg/day is effective in reducing the severity of motor symptoms in the OFF state. This suggests a continuous effect of rasagiline 1 mg/day throughout the day and night and is consistent with its extended duration of therapeutic action.

High prevalence of malignant melanoma in Israeli patients with Parkinson's disease.

The risk of melanoma is higher in patients with Parkinson's disease (PD) than in the general population. Whether the association is disease related or treatment related is unclear. The objective of this study was to assess melanoma prevalence in PD patients in Israel using active dermatologic screening. Consecutive patients with idiopathic PD were recruited by 12 Israeli centers. A movement disorder specialist assessed the severity of PD and obtained a medical, neurological, and medication history. Subsequently, a dermatologist assessed melanoma risk factors, recorded a dermatologic history, proactively performed a whole-body skin examination, and biopsied suspicious skin lesions. Of the enrolled patients (n = 1,395, mean age 69.5 ± 10.6 years, mean PD duration 7.3 ± 6.0 years), 95.3% were treated with dopaminergic agents. Biopsies revealed 8 patients with melanoma in situ and 1 with invasive malignant melanoma; 14 patients reported a melanoma prior to enrollment. The observed 5-year limited duration prevalence of melanoma in PD patients was 4.4 times greater (95% CI 2.6-7.6) than expected from melanoma prevalence in an age- and sex-matched cohort from the Israel National Cancer Registry. The increase was accounted for by an elevated prevalence of melanoma in situ [relative risk 12.5 (95% CI 6.7-23.2)]. Occurrence of melanoma did not correlate with levodopa therapy or time of onset of PD. Melanoma prevalence in PD patients was higher than expected in the general Israeli population. This was not related to levodopa treatment. PD patients should be actively screened for melanoma on a routine basis.

Long-term follow-up of patients with asymptomatic occlusion of the internal carotid artery with good and impaired cerebral vasomotor reactivity.

BACKGROUND: Cerebral hemodynamic status might be prognostic for either the symptomatic or asymptomatic course of carotid occlusive disease. It is determined by evaluating cerebral vasomotor reactivity (VMR). We assessed VMR in asymptomatic patients with total occlusion of the internal carotid artery (ICA) and followed them to evaluate the role of impaired VMR in predicting ischaemic stroke (IS). METHODS: Thirty-five patients (21 men, mean age ± SD 68 ± 7.5 years) with unilateral asymptomatic ICA occlusion were studied by transcranial Doppler and the Diamox test (intravenous 1.0 g acetazolamide) and followed for 48 months or until reaching the end-points of IS, transient ischaemic attack, or vascular death. VMR% was evaluated by recording the percent differences in peak systolic blood flow velocities in each middle cerebral artery at baseline and after Diamox administration. RESULTS: Based on VMR% calculations, 14 (40%) patients had good VMRs and 21 (60%) had impaired VMRs. The global annual risk of ipsilateral ischaemic events was 5.7%. The annual ipsilateral ischaemic event risk was 1.8% in patients with good VMRs, whilst it was 7.1% in patients with impaired VMRs. An impaired VMR was significantly correlated with ipsilateral IS (Kaplan-Meier log rank statistic, P = 0.04). CONCLUSIONS: Our results support the value of VMR assessment for identifying asymptomatic patients with carotid occlusion who belong to a high-risk subgroup for IS. New trials using extracranial-to-intracranial bypass surgery in patients with asymptomatic ICA occlusion and impaired VMRs are warranted.

Evolving pattern of Guillain-Barre syndrome in a community hospital in Israel.

OBJECTIVES: To investigate the frequency of axonal Guillain-Barre syndrome (GBS) in our ward over 6 years (1999-2005). MATERIALS AND METHODS: Clinical and electrophysiological findings of 40 patients admitted to neurology with abnormalities compatible with acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN) and acute inflammatory demyelinating polyneuropathy (AIDP) were reviewed. RESULTS: Electrophysiological findings showed that 25 (63%) patients had AIDP, nine (22%) AMAN and six (15%) AMSAN. There were significant differences in disease severity. Most axonal patients (87%) were hospitalized with moderate or severe symptoms (3-4 Hughes grade score) and progressed to severe grade (4-6) in comparison with AIDP patients (64% admitted with mild forms) (1-2 Hughes grade score) and progressed to severe in 44% of cases. Cranial nerve involvement was more frequent in AIDP (56%) in comparison with the axonal type (13%). Raised cerebrospinal fluid protein at the time of hospitalization was observed in 76% of demyelinating and 33% of axonal patients. CONCLUSIONS: Axonal GBS occurred more frequently in Israel compared with other Western countries.

Low dose methylphenidate improves freezing in advanced Parkinson's disease during off-state.

Five men with advanced idiopathic Parkinson's disease (PD) were examined to assess the effect of low dose methylphenidate (MPD) on gait. The patients were tested during "off" state before and two hours after the intake of 10 mg MPD while walking an "8 trajectory". The total walking time, total freezing time, number of freezing episodes and the non-freezing walking time were assessed. The obtained data were compared by the Wilcoxon Signed Rank test with a type I error rate of 0.05. The results showed a statistically significant improvement in all gait parameters after MPD intake. Moreover, a good correlation in the grade of improvement for each individual gait characteristic was found. The study demonstrates that low dose of MPD may improve gait, and especially freezing, in patients with severe PD, without the need for exogenous L-dopa. The mechanism of MPD action in patients with advanced PD is further discussed.

The effect of quetiapine in psychotic Parkinsonian patients with and without dementia. An open-labeled study utilizing a structured interview.

OBJECTIVES: We studied the effect of quetiapine in drug induced psychosis (DIP) in Parkinson's disease (PD) patients with dementia (PDDEM) and without dementia (PDNODEM) in a 6-month open study. METHODS: Thirty five consecutive PD patients with DIP (19 of them demented [DSMIV criteria]) were examined. Assessment included Mini-Mental State Examination (MMSE), UPDRS (motor part), Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGIS) and Hamilton test (for depression). Quetiapine was administered in a flexible dose 25-600 mg daily. Out of the 35 patients included in the study, 24 completed treatment with quetiapine (14 demented and 10 without dementia). Treatment was stopped in 11 patients (5 demented). RESULTS: Intention to treat patient (ITT) analysis did not show a significant quetiapine effect (BPRS), although in about 30% a good outcome was reported by the family (CGIS). Among the patients who completed the study (n = 24), in the PDNODEM group (n = 10) BPRS improved almost significantly (p = 0.06) while in the PDDEM group the BPRS did not change. According to the CGIS, a good improvement was observed in 50% of the PDDEM group (7/14) and 40% of the PDNODEM group (4/10). Motor features of PD patients worsened mildly (p = 0.05) in the PDDEM group. CONCLUSION: In this open trial, quetiapine was not beneficial in the ITT group using the BPRS, although families reported improvement in about 30% of patients (CGIS). Among patients who completed the study, quetiapine was more effective in the PDNODEM group. A double blind study with quetiapine is required.

The effects of acute loading with levodopa and levodopa with selegiline on blood pressure and plasma norepinephrine levels in chronic Parkinson's disease patients.

OBJECTIVES: Contradictory possible cardiovascular side effects of selegiline have been reported. Therefore, we studied the effect of acute administration of selegiline with levodopa (LD) compared with LD alone, on blood pressure, pulse and norepinephrine (NE) plasma levels, during an orthostatic test on chronically treated Parkinson's disease patients (PDpts) and controls. MATERIALS AND METHODS: Twelve PDpts treated with LD (group D), 12 PDpts treated with selegiline and LD (group S) and eight volunteers (CTRL) underwent the orthostatic test. Patients repeated the test twice, before and after acute loading with 125 mg LD (group D) and 125 mg LD +5 mg selegiline (group S). RESULTS: Group S showed more episodes of postural hypotension (n = 10; two symptomatic) than group D (n = 4) and CTRL (n = 2), however not statistically significant. Plasma NE also rose significantly higher (P < 0.001) in group S. CONCLUSION: PD patients treated with selegiline showed more orthostatism and higher plasma NE after submission to the orthostatic test. These findings may be relevant to explain its deleterious effect.

Polysomnography in patients with intracranial tumors before and after operation.

OBJECTIVE: To evaluate the breathing and sleep patterns in patients with brain tumors before and after operation, and assess their relation to the location and size of the tumor, as well as to the post-operative outcome. METHODS: Polysomnographic studies were performed in 11 patients with intracranial tumors (nine supra- and two infratentorial) before and after surgery. RESULTS: Pre-operatively, the mean apnea-hypopnea index (AHI) was 23.3. Six patients demonstrated signs of obstructive sleep apnea (SA) and one had mixed obstructive and central type SA. After operation, the mean AHI decreased to 8.1(P < 0.05). The duration of random eye movement sleep stage increased after tumor removal (P < 0.04). No relation was found between the characteristics of the tumor, nor the post-operative outcome and SA. CONCLUSIONS: Patients with brain tumors often suffer from SA and this can further worsen their symptoms related to increased intracranial pressure. Removal of the tumor results in a substantial decrease in sleep-related disturbances and may thus play a role in clinical recovery.

Electroencephalography findings in adult patients with West Nile virus-associated meningitis and meningoencephalitis.

Eighteen adult patients with serologically confirmed West Nile virus (WNV)-associated meningitis or meningoencephalitis were admitted to our hospital during the 2000 West Nile fever outbreak in Israel. Thirteen of the patients had a more severe and prolonged clinical course, and an electroencephalogram (EEG) was, therefore, requested. A specific EEG pattern was seen in 8 patients, consisting of generalized slowing, which was more prominent over the anterior regions. Generalized slowing that was prominent over the temporal area was seen in 2 patients, and intermittent slowing over the temporal region was seen in 1 patient. Two patients had normal EEG findings. We suggest that WNV meningoencephalitis should be considered in the differential diagnosis of meningitis or meningoencephalitis with a prolonged clinical course and anteriorly predominant slowing on an EEG.

Periodic lateralized epileptiform discharges in multiple sclerosis: a case report.

The occurrence of epileptiform abnormalities on the EEG in patients with multiple sclerosis (MS) is rare. The following case correlates the clinical, EEG, MRI, and single photon emission computed tomographic (SPECT) findings in a patient with a long history of MS and acute onset of focal motor seizures and confusion. Two routine EEGs, brain MRI, and brain SPECT were performed. The patient was a 44-year-old woman with a long history of clinically definite MS of the relapsing-remitting and secondary progressive form with three events of focal motor seizures followed by generalized tonic-clonic seizures and postictal confusion. The first EEG done during admission showed periodic lateralized epileptiform discharges in the right temporal region. Brain MRI done several weeks later showed scattered T2 hyperintensities in several locations, including the periventricular and subcortical white matter bilaterally. Brain SPECT using Tc99-Neurolite demonstrated decreased perfusion on the right parietal and temporal lobes. This case suggests that focal motor seizures and a transient state of altered consciousness can be the result of an exacerbation of MS. The neurophysiologic expression of these clinical manifestations may present as periodic lateralized epileptiform discharges on the EEG and decreased regional perfusion on brain SPECT.

The clinical use of P300 event related potentials for the evaluation of cholinesterase inhibitors treatment in demented patients.

Centrally acting cholinesterase inhibitors (ChEIs) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment methods such as standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response would be most helpful.Thirty-two patients suffering from dementia of several etiologies were treated with ChEIs (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed pre ChEIs initiation (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), Alzheimer's disease assessment scale cognitive part (ADAS-cog) and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4, n = 31 to 27.4, n = 29; p = 0.08) while MMSE remained almost unchanged (20.1, n = 29 to 19.8, n = 28). Mean P300 latency reduced significantly by 24 ms (from 383 +/- 7.9 msec, n = 32 to 359 +/- 7 msec, n = 32; p = 0.0001). However mean amplitudes did not change significantly from baseline to endpoint (13.5 +/- 6.2, n = 31 to 12.8 +/- 6.1, n = 31). Significant correlations were found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.485 p = 0.019, R = 0.626 p = 0.001 respectively, n = 23) and between mean MMSE and P300 latency at baseline and endpoint (R = -0.420 p = 0.046, R = -0.703 p < 0.001 respectively, n = 23). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEIs in demented patients.

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.

Comparison of glatiramer acetate (Copaxone) and interferon beta-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.

[Diagnosis of idiopathic autonomic neuropathy].

This is a case report of a 51 years old woman admitted to the hospital due to abdominal pain and intractable diarrhea of two months duration. Her history and her physical examination revealed signs and symptoms leading to the diagnosis of the rare syndrome of idiopathic autonomic neuropathy. In this case report we briefly describe the characteristics of the syndrome and its natural history and treatment. We also raise the important issue of common error patterns in diagnostic reasoning such as "omission" and "anchoring" and how these patterns are reflected in the present case.

H reflex behavior in Parkinson's disease patients and patients with extrapyramidal and pyramidal signs combined.

The H reflex was elicited in 21 normal subjects, 48 patients with Parkinson's disease (PD) and 22 patients with pyramidal and extrapyramidal signs combined (PESC). In most normal subjects (90.5%), in 29.2% of PD patients and 54.5% of patient with PESC the threshold for sensory fibers was lower than for motor fibers, and the H reflex was obtained before the M response for all duration stimuli in both legs. In 9.5% of normal subjects, 39.6% of PD patients with mild and moderate rigidity (according to the motor part of UPDRS) and 31.8% of patients with PESC, the threshold for the H reflex and M response was the same or the M response threshold was lower in at least one of the legs for short stimulus duration (0.1-0.2 ms). In 31.2% of PD patients (most of them with severe rigidity) and 13.7% of patients with PESC, the threshold for M response was lower for all stimulus duration in at least one of the legs, and it was obtained before H reflex. These very significant differences in behavior of the H reflex in PD patients (Fisher exact test, p<0.0001) that almost disappear in patients with PESC, could be possibly explained by changes in agonist-antagonist inhibition.

The polyamine stress response: tissue-, endocrine-, and developmental-dependent regulation.

Transient alterations in polyamine (PA) metabolism, termed the polyamine stress response (PSR), constitute a common cellular response to stressful stimuli. In contrast to the adult brain and liver, the PSR in the adrenal gland and thymus is characterized by a reduction in PA metabolism. The brain PSR undergoes an early postnatal period of non-responsiveness. The aim of the present study was twofold: i) to determine whether the PSR in the liver, thymus, and adrenal gland is developmentally regulated as that in the brain and ii) to establish whether neuronal and hormonal signals can activate the PSR independently. Ornithine decarboxylase (ODC) activity and tissue PA concentrations served as markers of the PSR. Changes were measured in male Wistar rats during postnatal development and at 2 weeks after adrenalectomy in adults. Unlike the brain, the direction of the PSR in peripheral organs did not undergo developmental changes. After adrenalectomy, the PSR was not activated in the thymus and liver by acute (2-hr) restraint stress, but a characteristic PSR was induced in the hippocampus. However, dexamethasone injection (3 mg/kg) did induce a characteristic PSR in all organs of adrenalectomized rats. The results justify the following conclusions: i) Unlike peripheral organs, the PSR in the brain is developmentally regulated; ii) The developmental switch to a mature PSR in the brain corresponds in time to the cessation of the "stress hypo-responsive period" in the hypothalamic-pituitary-adrenocortical (HPA) axis; iii) In the periphery, the PSR appears to be dependent principally on stress-induced activation of the HPA axis and on increased circulating glucocorticoid concentrations rather than on neuronal activation; iv) In the brain, however, the PSR can be induced independently by glucocorticoids or by direct activation of the neuronal circuitry; and v) up-regulation of the PSR, as in the brain and liver, is constructive and may be implicated in cell survival, while its down-regulation, as in the adrenal and thymus, may be implicated in cell death.

Evaluation of cholinergic treatment in demented patients by P300 evoked related potentials.

Centrally acting cholinesterase inhibitors (ChEls) improve cognitive functions in Alzheimer's disease (AD) and other forms of dementia. Evaluation of treatment efficacy is based mainly on subjective assessment tools which includes standardized neuropsychological tests. Therefore, an additional objective tool for the evaluation of drug response is necessary. Thirty two patients were treated with ChEls for dementia (tacrine 19, donepezil 5, rivastigmine 8). Cognitive response was assessed before ChEls (baseline) and after 26 weeks, as optimal tolerated doses were achieved and maintained (endpoint). Evaluation included repeated measurements of Mini Mental State Examination (MMSE), ADAS-cog and P300. For statistical analysis we used ANOVA with repeated measures and Pearson correlation coefficient. Results demonstrated improvement of mean ADAS-cog by 2.0 points (from 29.4 to 27.4 p = 0.08) while MMSE remained almost unchanged (20.1 to 19.8). Mean P300 latency reduced significantly by 24 msec (from 383 msec to 359 msec, p = 0.0001) thus reflecting the clinical improvement. However mean amplitudes did not change from baseline to endpoint (13 microvolts). Significant correlation was found between mean ADAS-cog and mean P300 latency at baseline and end-point (R = 0.452 p = 0.014, R = 0.567 p = 0.001 respectively). Strong correlation was found between mean MMSE and P300 latency at Baseline (R = -0.335 p = 0.07), and significant correlation was found at endpoint (R = -0.613 p < 0.001). Our data suggests that P300 is a reliable instrument for assessment of cognitive response to ChEls in demented patients.

The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia.

Patients suffering from Parkinson's disease (PD), often develop dementia (PDD). Their brain histology reveals Alzheimer's disease (AD) like changes and decreased cholin-acetyl transferase (ChAT) activity, in addition to typical PD changes. This cholinergic deficiency has been related to the degree of mental decline. As centrally acting cholinesterase inhibitors (ChEIs) provide cognitive and non-cognitive improvement for AD patients, the same therapeutic effect was hypothesized for PDD patients as well. The goal of this study was to assess the effect of ChEIs on both the cognitive and motor state of PDD patients. An open study was conducted. Eleven consecutive PDD patients (M/F 6/5 mean age 75 y) were found eligible for inclusion. They were treated for 26 weeks with tacrine (7 patients) and donepezil (4 patients) as add-on to their regular anti PD drugs. Cognitive assessment was performed at baseline and endpoint by Mini-Mental-State-Examination (MMSE) and Alzheimer's-Disease-Assessment-Scale (ADAS-cog). Global Deterioration Scale (GDS) was performed to evaluate active daily living (ADL). Motor evaluation was performed using Short Parkinson Evaluation Scale (SPES) at baseline and end-point. Statistical analysis used Student's paired t-test, ANOVA with repeated measures and Pearson correlation coefficient. ChEIs treated PDD patients showed improvement in their cognitive state. Mean ADAS-cog improved significantly by 3.2 points (p < 0.012). Mean MMSE and GDS improved non-significantly by 1.2 and 0.2 points respectively. There was no change in motor function as evident by mean SPES scores, 16.5 at baseline and endpoint. Five individuals actually demonstrated motor improvement under ChEIs. We conclude that ChEIs have a beneficial effect on the cognitive state of PDD patients without aggravating motor function.