Differences in diagnosis, follow-up and treatment of patients with dementia living in the peripheral areas compared with the central areas of Israel.

We compared data regarding diagnosis, treatment and follow-up of patients with dementia in the central and the peripheral areas of Israel. Data were collected from the medical records of 164 patients with advanced dementia, all residents of dementia special care units - 97 patients from a central nursing home and 67 patients from the peripheral areas. The data collected related to the period prior to hospitalization and included: demographic data, imaging tests, follow-up by a memory clinic and drug treatment prior to admission. Mini Mental State Examination on admission was also recorded. Patients in the peripheral areas were hospitalized while having better cognitive function, as demonstrated by the Mini Mental State Examination (p < 0.05). More patients in the central areas versus the peripheral areas were aided by an in-house worker prior to admission (p < 0.001). More patients with dementia in the central areas were followed up by a memory clinic (p < 0.001) and underwent brain imaging (p < 0.01) compared with patients with dementia living in the peripheral areas. Although not significant, patients from the central areas were more commonly treated with atypical neuroleptics for behavioral problems (p = 0.05). On the basis of the current data, we suggest that there are differences in the diagnosis, follow-up and drug treatment among patients with dementia living in the central areas versus those living in the peripheral ones. Patients in the peripheral areas are hospitalized while their cognitive abilities are relatively better than those of the patients in central areas.

Prevalence of primitive reflexes and Parkinsonian signs in dementia.

OBJECTIVE: Primitive reflexes and parkinsonian signs are used by clinicians to differentiate among dementias. We reviewed our clinical sample to determine whether primitive reflexes were more prevalent in frontally-based dementias and whether parkinsonian signs were more common in dementia with Lewy bodies (DLB) than in other types of dementia. DESIGN: We retrospectively reviewed charts from 204 patients with dementia who presented for consultation at Baycrest's Ross Memory Clinic between April, 2003, to December, 2007. RESULTS: A greater proportion of subjects with DLB and dementia of the Alzheimer type with cardiovascular disease had primitive reflexes than subjects with frontotemporal dementia (FTD). Primitive reflexes were not positively predictive of FTD or vascular dementia (VaD). Dementia with Lewy bodies subjects were more likely to have parkinsonian signs than the other dementias, and bradykinesia and rigidity were positively predictive of FTD. The palmomental reflex was the most common primitive reflex in the sample, and cogwheeling was the most common parkinsonian sign. There was no significant difference between early- and late-stage groups in presence of primitive reflexes or parkinsonian signs. CONCLUSIONS: Primitive reflexes appear not to be clinically discriminative of frontally-based dementias such as FTD and VaD.

Subjective memory decline in healthy community-dwelling elders. What does this complain mean?

OBJECTIVES: Subjective feelings of memory decline are fairly common among the elderly. The causes of this are heterogeneous, and may be related to both affective and cognitive disorders. We attempted to explore the associations between subjective and cognitive measures. MATERIALS AND METHODS: Healthy subjects were studied. They completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression scale (GDS), and the Spielberger State-Trait Anxiety Inventory. Cognitive functions were tested using the Mini-Mental State Exam and supplemented with NeuroTrax, a computerized neurophysiological battery. Univariate logistic regression model was applied to estimate odd ratios (OR) and 95% confidence intervals of associations. RESULTS: Of 341 consecutive non-depressed subjects, 257 participants (75.4%) reported subjective memory decline (SMD). Subjects with and without SMD did not differ in age, gender, education, marital status, employment and life-style. Subjects with SMD had elevated GDS scores (OR = 1.14, 95% CI: 1.003-1.29), white anxiety level showed a tendency to be increased (OR = 1.03, 95% CI: 0.99-1.06). Comparison of cognitive performance has not revealed differences in cognitive domains between subjects with and without SMD. CONCLUSIONS: SMD in healthy elderly people is associated with sub-clinical depression even among those without objectively measured cognitive decline.

Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease.

BACKGROUND: It was commonly assumed that psychotic phenomena in Parkinson's disease (PD) are mainly drug related. Accumulating evidence suggests the existence of other risk factors for psychosis in PD. Aims. To evaluate the contribution of the drug profile of patients with PD to emergence of hallucinations. METHODS: We compared patients with and without hallucinations, using Cox proportional hazards model, concerning drug profile at the time of hallucinations emergence. RESULTS: Of 422 consecutive patients, 113 had dementia, while 90 patients experienced hallucinations (46 had both dementia and hallucinations). The mean levodopa dose for the group of patients with hallucinations was 650 +/- 279 mg/day at the time of hallucinations onset, which was not significantly different from the levodopa dose at last visit for the group without hallucinations (621 +/- 326 mg/day). Supplementary treatment with amantadine, selegiline, dopamine agonists, entacapone and anticholinergics did not increase the risk for the development of hallucinations. CONCLUSIONS: We did not confirm drug treatment as a risk factor for hallucinations in PD. Our study suggests the existence of "endogenic" factors as substantial contributors in the genesis of PD hallucinations. The clinical implications may be earlier administration of antipsychotic treatment and not as traditionally accepted, dose reduction of antiparkinsonian drugs.

The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias. Potential therapeutic approaches.

Dyskinesias are the most frequent adverse effect of chronic levodopa therapy in patients with Parkinson's disease (PD). Current pharmacological treatment for this problem is unsatisfactory. Recently, there is evidence for the role of glutamate in the basal ganglia neuronal circuitry in the generation of dyskinesias. If indeed glutamatergic overactivity beyond the dopaminergic synapses plays a role in the pathogenesis of these involuntary movements, there is hope that its suppression may be beneficial without causing loss of levodopa efficacy and parkinsonian deterioration. Indeed, NMDA receptor antagonists such as amantadine and dextrometorphan can reduce such dyskinesias. We tested the efficacy of riluzole, an inhibitor of glutamatergic transmission in the inhibition of levodopa-induced dyskinesias.

Daily migraine with aura: a new migraine variant.

The frequency of migraine attacks is not used as a diagnostic criterion, however, it is a very important factor in the evaluation of migraine severity and its treatment. Several studies report the frequency of migraine attacks using the International Headache Society criteria. No investigator, however, has reported daily migraine attacks. In the current report, we present five patients whose headaches transformed from episodic migraine to daily migraine with aura. To the best of our knowledge, this is the first description of this variant of migraine. The symptoms in all the patients described comply strictly with the International Headache Society criteria for the diagnosis of migraine with typical aura. An interesting additional observation concerns the beneficial effect of phenytoin, a drug that has not proved to be effective in migraine but showed some efficacy in our patients.

Mice overexpressing Bcl-2 in their neurons are resistant to myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE).

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by destruction of myelin. Recent studies have indicated that axonal damage is involved in the pathogenesis of the progressive disability of this disease. To study the role of axonal damage in the pathogenesis of MS-like disease induced by myelin oligodendrocyte glycoprotein (MOG), we compared experimental autoimmune encephalomyelitis (EAE) in wild-type (WT) and transgenic mice expressing the human bcl-2 gene exclusively in neurons under the control of the neuron-specific enolase (NSE) promoter. Our study shows that, following EAE induction with pMOG 35-55, the WT mice developed significant clinical manifestations with complete hind-limb paralysis. In contrast, most of the NSE-bcl-2 mice (16/27) were completely resistant, whereas the others showed only mild clinical signs. Histological examination of CNS tissue sections showed multifocal areas of perivascular lymphohistiocytic inflammation with loss of myelin and axons in the WT mice, whereas only focal inflammation and minimal axonal damage were demonstrated in NSE-bcl-2 mice. No difference could be detected in the immune potency as indicated by delayed-type hypersensitivity (DTH) and T-cell proliferative responses to MOG. We also demonstrated that purified synaptosomes from the NSE-bcl-2 mice produce significantly lower level of reactive oxygen species (ROS) following exposure to H2O2 and nitric oxide (NO) than WT mice. In conclusion, we demonstrated that the expression of the antiapoptotic gene, bcl-2, reduces axonal damage and attenuates the severity of MOG-induced EAE. Our results emphasize the importance of developing neuroprotective therapies, in addition to immune-specific approaches, for treatment of MS.

Camptocormia (bent spine) in patients with Parkinson's disease--characterization and possible pathogenesis of an unusual phenomenon.

Camptocormia is characterized by severe forward flexion of the thoracolumbar spine which increases while walking and disappears in the recumbent position. We describe for the first time eight patients with presumed idiopathic Parkinson's disease (mean age 66+/-5 yrs; mean symptom duration 13.1+/-5.1 yrs) who developed camptocormia. This impressive abnormal posture emerged 4-14 years from disease onset, and in some patients stooped posture was the prominent symptom at diagnosis. There was no clear correlation between camptocormia and levodopa treatment. In some patients the camptocormic posture improved, and in others it was unchanged or even aggravated following levodopa administration. Three patients reported worsening of this symptom during "off" periods and also with fatigue. The pathogenesis of this phenomenon is unknown but might represent either a rare type of dystonia or an extreme form of rigidity.

[Apomorphine for treatment of "off-periods" in Parkinson's disease].

After 3-5 years of continuous use of 1-dopa preparations for Parkinson's disease, 25%-50% of patients develop side-effects such as the "on-off" phenomenon and involuntary movements that markedly impair function. One cause of these manifestations is evidently a disturbance in the absorption of 1-dopa. We attempted to avoid this problem by using subcutaneous injections. Apomorphine is a rapid-acting dopamine agonist which causes a return from "off" to "on" within minutes. We present the results of a trial of subcutaneous injections of apomorphine in 22 Parkinsonian patients (12 males, 10 females) with severe motor fluctuations. During 5 days prior to the apomorphine all received Motilium (domperidone, 60 mg/d) to prevent nausea and vomiting. All were hospitalized initially to determine optimal dosage and to teach them the technique of self-injection. 2 to 4 mg of apomorphine were injected 1 to 3 times daily for 2 to 12 months. In 17 patients (80%) "off" periods were reduced without significant side-effects. Apomorphine seems to be effective, tolerable treatment for shortening 1-dopa induced "off" periods.

[Embolic splenic infarction: a rare complication of atrial fibrillation].

Splenic infarction is a rare disorder. The typical clinical presentation is sudden pain in the left upper quadrant of the abdomen, and awareness to this possibility is the major clue for diagnosis. We describe a 49-year-old man with chronic atrial fibrillation and splenomegaly who was treated with anticoagulants. Because of hematuria, the regular dose of anticoagulant therapy was reduced. The hematuria stopped but he complained of sudden onset of pain in the left upper quadrant. Computerized tomography and isotope scan of the spleen confirmed the clinical suspicion of splenic infarction. Treatment with anticoagulants and analgesics was followed by clinical improvement.

Machado-Joseph disease: correlation between the clinical features, the CAG repeat length and homozygosity for the mutation.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a CAG trinucleotide repeat in the MJD1 gene located on 14q32.1. We confirmed that the CAG expansion caused MJD in a Yemenite Jewish family and demonstrated that most of the clinical variation among members of this family was due to the genotype of the affected individuals. Six patients who presented with an early onset (25 years) and severe disorder were found to be homozygous for the CAG expansion. Among 5 heterozygotes for the CAG expansion older than 40 years, one had neurological symptoms from the age of 45, while the others were asymptomatic. In one of the heterozygotes, no neurological symptoms were present when last examined at the age of 66. Homozygosity for the MJD1 mutation was the main cause of variability in this large family, however, other factors clearly played a role in the expression of the gene. We could demonstrate that homozygote sibs with similar expansion in both alleles had significant differences in disease severity. Gender did not affect the clinical expression in this family.