Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Disease--Results of a Phase I Study.

OBJECTIVE: The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. DESIGN: A 1-year phase I proof-of-concept study. SETTING: The Department of Psychiatry and Psychotherapy at the University of Cologne. PARTICIPANTS: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. INTERVENTION: Bilateral low-frequency DBS of the nucleus basalis of Meynert. MEASUREMENTS: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. RESULTS: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042). CONCLUSION: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

[A case of Bleuler's disease? 100 years of dementia praecox or group of schizophrenias]. / Ein Fall von Morbus Bleuler? : 100 Jahre "Dementia praecox oder Gruppe der Schizophrenien"

Approximately 100 years ago Eugen Bleuler published the most significant contribution to psychiatry by conceptualizing the term schizophrenia as a diagnostic entity. In modern diagnostic manuals Bleuler's concept is only reflected in subordinated criteria, i.e. the negative symptoms. On the occasion of the anniversary of Bleuler's essential publication, the present work aims to exemplify the differences in diagnostic concepts and it will be illustrated that Bleuler's intention to establish his so-called basic symptom as a guideline for diagnostics has to be considered as failed from a present day viewpoint.

Extrapyramidal signs, primitive reflexes and incontinence in fronto-temporal dementia.

According to the diagnostic consensus criteria [1] akinesia, rigidity and tremor as well as primitive reflexes and incontinence support the diagnosis of fronto-temporal dementia (FTD). However, the prevalence of extrapyramidal signs (EPMS), primitive reflexes and incontinence in FTD has not yet been systematically studied. In the present study, thirty-one patients with mild or moderate FTD without previous or present antipsychotic medication underwent a detailed neurological exam including the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). The average total score on the motor subscale of the UPDRS was 14.0 points. Akinesia and Parkinsonian gait or posture were found frequently but were mild in most instances. Rigidity was found in 36% of the patients. Resting tremor was a rare symptom. The only primitive reflex that occurred was a positive palmomental that was found in 7% of the patients. Urinary incontinence was present in 26%. The results have to be confirmed with larger or pooled patient samples from different ascertainment scenarios. If the results of the present study can be replicated, a revision of the consensus criteria from 1998 might be considered.

The role of alpha-synuclein gene multiplications in early-onset Parkinson's disease and dementia with Lewy bodies.

BACKGROUND: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families. METHOD: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe. RESULTS: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein. Mutational screening of the entire coding region of alpha-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case. CONCLUSIONS: Thus, this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.

Primary central nervous system lymphoma in the SMA presenting as rapidly progressive parkinsonism.

We report on a 56-year-old man who developed a rapidly progressive parkinsonism and apraxia over 2 months due to biopsy confirmed cerebral non-Hodgkin lymphoma primarily involving the SMA and parts of the superior frontal gyrus bilaterally.

[Brain stem and cerebellar atrophy in neurosyphilis]. / Hirnstamm- und Kleinhirnatrophie bei Neurosyphilis.

A 54-year-old man suffered from serologically proven neurosyphilis with tetraspastic syndrome and bladder dysfunction. He showed a pronounced psychopathy with cognitive decline and attention/concentration deficits. MRI showed slowly progressive cerebellar and brainstem atrophy, which has rarely been described over the past decades. During times of higher incidence and prevalence of neurosyphilis, infratentorial atrophy had been described occasionally, but today this clinical manifestation has been all but forgotten.

Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease.

Dysfunction of the blood-cerebrospinal fluid barrier (BCB) has been implicated in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. Therefore, we assayed serum and cerebrospinal fluid (CSF) from 30 parkinsonian patients and 30 controls for concentrations of albumin and IgG. The CSF/serum ratio for albumin (AQ), IgG (GQ), IgG-index as well as determination of oligoclonal bands were used to evaluate BCB function and to quantify humoral immune response within the central nervous system (CNS). Levels of AQ, GQ and IgG-index did not significantly differ in both groups. We found no dysfunction of the blood-CSF barrier or signs of local synthesis of IgG in the central nervous system of parkinsonian patients. Our data do not support the hypothesis of a dysfunctional BCB that contributes to pathophysiological mechanisms underlying PD.

Effect of echo contrast media on the visualization of transverse sinus thrombosis with transcranial 3-D duplex sonography.

Transcranial duplex sonography has the capacity of detecting venous flow as in the transverse sinus. During a 6-month period, 28 consecutive patients (mean age 55 y) with a clinically suspected diagnosis of cerebral sinus thrombosis were included in the study. All patients were examined using 3-D ultrasound equipment within 24 h of having undergone either venous computerized tomography (CT), venous magnetic resonance imaging (MRI) or cerebral angiography. A total of 22 healthy patients had a normal venous CT, venous MRI or cerebral angiography of both transverse sinuses. Before echo contrast enhancement, the transverse sinus could be visualized in only 2 of these 44 sinuses (22 patients). A total of 6 patients with an unilaterally missed transverse sinus in 3-D ultrasound suffered from sinus thrombosis (n = 3), hypoplasia (n = 2) or aplasia (n = 1) of the unilateral transverse sinus in neuroradiological tests. In none of the patients with an thrombosis of the transverse sinus did ultrasound contrast media application improve the visualization of the affected sinus. Our study confirms that the normal transverse sinus, insonated through the contralateral temporal bone, often cannot be visualized without the use of contrast agents. With transcranial 3-D duplex sonography, a differentiation between thrombosis, hypoplasia and aplasia of the sinus was not possible.

R- and S-salsolinol are not increased in cerebrospinal fluid of Parkinsonian patients.

Various investigators address an augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL), or an increased N-methylation of these compounds as putative pathophysiologic mechanisms in Parkinson's disease (PD). Objectives of this study were (1) the evaluation of a putative elevation of enantiomers (R-, S-) of SAL and (2) the investigation of relations between these metabolic precursors of neurotoxic N-methylated-SAL (NMSAL) and dopamine in cerebrospinal fluid of untreated de-novo Parkinsonian patients and age- and sex-matched healthy controls. Levels of R- and S-SAL and dopamine did not significantly (R-SAL: P = 0.75, S-SAL: P = 0.69, dopamine: P = 0.46) differ and dopamine did not correlate to R-SAL and S-SAL in both groups. We conclude, that central accumulation of R-NMSAL, which is neurotoxic to dopaminergic nigrostriatal neurons, is not due to elevated synthesis of R-SAL and/or S-SAL in PD.

[Neurocysticercosis. Current review of the literature based on a long-term study of 2 clinically distinct German cases]. / Neurozystizerkose. Aktuelle Literaturübersicht anhand einer Langzeitbeobachtung zweier klinisch distinkter deutscher Erkankungsfälle.

Neurocysticercosis, caused by Taenia solium larvae (cysticerci), is the most common parasitic infection of the human CNS Worldwide. In Germany its appearance is rare. Here we report two cases of neurocysticercosis which we followed over a period of 4-6 years. The first patient acquired neurocysticercosis in Germany. On admission he suffered from papilledema, partial seizures and a mild psychotic disorder. MR-tomography showed an internal hydrocephalus and multiple contrast enhancing parenchymal cysts. In the course of the disease a giant cyst within the left temporal pole developed and was exstirpated neurosurgically. The persistent internal hydrocephalus required ventriculoperitoneal shunting. Therapy with Praziquantel led to a clinical improvement, however, repeated analysis of the cerebrospinal fluid documented persistent inflammation. With the aid of a contrast enhanced three-dimensional (3D) ultrasound imaging technique we demonstrated increased cerebral perfusion surrounding one cyst. This may be interpreted as evidence for persistent disease activity. The second patient presented with repeated episodes of cysticercotic encephalitis, which is rarely described in the literature (incidence 1%). Clinical features, laboratory findings, diagnosis, and therapy of neurocysticercosis will be presented together with the pitfalls of the two described cases. Our cases will be compared to previous reports on clinical findings in neurocysticercosis.

Plasma levels of R- and S-salsolinol are not increased in "de-novo" Parkinsonian patients.

An augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL) or an increased N-methylation of these compounds has been addressed by various investigators as putative pathophysiologic mechanisms in Parkinson's disease (PD). Aim of this study was (1) to investigate putative relations between plasma levels of dopamine and R- and S-enantiomers of SAL and (2) whether these metabolic precursors of the neurotoxic N-methylated-SAL (NMSAL) are elevated in untreated "de-novo" Parkinsonian patients compared to age- and sex-matched healthy controls. Plasma levels of R- and S-SAL and dopamine did not significantly (R-SAL: p=0.61, S-SAL: p=0.51, dopamine: p=0.84) differ in both groups. Parkinsonian patients' R-SAL plasma levels were inversely related to intensity (p=0.03, r =-0.42) and duration of PD (p=0.03, r=-0.43) in contrast to S-SAL and dopamine. Dopamine levels were not associated to R-SAL (p=0.88, r2=0.0008) and S-SAL (p=0.088, r2=0.12) neither in Parkinsonian patients nor in controls. We conclude, that an upregulation of N-methylation of tetrahydroisoquinolines takes place in PD by enzymes such as neutral N-methyltransferase specific for R-SAL. The activity of this enzyme has been found elevated in parkinsonian lymphocytes. This increased N-methylation by the N-methyltransferase specific for R-SAL leads to the known augmented levels of neurotoxic R-NMSAL in Parkinsonian patients compared to controls in the cenral nervous system especially in the beginning of PD.