Amino acid supplementation in l-dopa treated Parkinson's disease patients.

BACKGROUND: The correlation between Parkinson disease and malnutrition is well established, however a protein-restricted diet is usually prescribed because of potentially negative interactions between dietary amino acids and l-dopa pharmacokinetics. This strategy could increase the risk of further nutritional deficits. METHODS: A monocentric, prospective, randomized, double-blind pilot study was performed on two groups of Parkinson-affected, protein-restricted, patients: Intervention (n = 7; amino acid supplementation twice daily) and Placebo (n = 7; placebo supplementation twice daily). At enrolment, after 3- and 6-month supplementation, neurological evaluations (UPDRS III, Hoenh-Yahr scale, l-dopa equivalent dose assessment) were performed and blood sample was collected to define insulin sensitivity (QUICKI index) and oxidative stress (oxidized and reduced glutathione). Repeated measure ANCOVA was applied to define time effect and time × treatment interaction. RESULTS: Participants were comparable at baseline for all assessed parameters. Neurological outcomes and l-dopa requirement were comparable in both group after 6-month of supplementation, without time × treatment interaction. The decrease in insulin sensitivity, as assessed by QUICKI index, observed after 6 months in both groups, was greater in Placebo than in Intervention (time effect p < 0.001; time × treatment interaction p = 0.01). Moreover, despite no changes in total erythrocyte glutathione concentrations, oxidized glutathione levels decreased by 28 ± 17% in the Intervention while increased by 55 ± 38% in Placebo (time effect p = 0.05; time × treatment interaction p = 0.05), after 6-month supplementation. CONCLUSIONS: Amino acid supplementation, assumed with shrewd temporal distribution, did not show detrimental effects on neurological and pharmacological control in protein-restricted Parkinson-affected patients, chronically treated with l-dopa. Furthermore, daily amino acid supplementation partially counteracted insulin resistance development and the loss in antioxidant availability.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue.

PURPOSE: This study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue. MATERIALS AND METHODS: We enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05). RESULTS: Compared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex. CONCLUSIONS: Patients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.

18F-FDG-PET/CT.

[18F]FDG has been the first radiopharmaceutical used for human brain PET studies and still is the most used radiotracer worldwide for PET and PET/CT oncologic applications. In the assessment of brain tumors, in spite of its low sensitivity in some histological exams, chiefly low-grade lesions, its prognostic value remains of high clinical impact. Moreover, the reliability of [18F]FDG in examining not only the tumor itself, but also the functional state of the whole brain, makes this tracer a valuable tool for treatment decisions and patient management, even nowadays when new tracers (especially amino-acids) are available. In addition, [18F]FDG has a role in the differential diagnosis between relapse and necrosis when assessing aggressive tumors and to establish dedifferentiation in low-grade lesions. With the growing of available therapies, another emerging application of [18F]FDG is the monitoring of response to treatment, even though more evidence is needed to assess the best scanning time. Finally, the implementation of CT in PET devices most likely will improve the sensitivity and specificity of [18F]FDG, even though more data are needed to better understand which is the real advantage of PET/CT with respect to multimodality imaging. Currently, the possible added value of PET/CT is in the study of secondary brain lesions. It is believable that in the future we will keep on speaking about this "old" radiotracer, still alive.

A case of hypocalcemia-related epilepsia partialis continua.

Epilepsia partialis continua (EPC) is a syndrome clinically defined as continuous spontaneous jerking confined to one part of the body, sometimes aggravated by action or sensory stimuli, occurring over hours, days or even years. In adults the more frequent recognized cause of EPC is an acute cerebrovascular disease. Acute severe hypocalcemia is a highly epileptogenic ionic disturbance, abnormally increasing neuronal excitability. In this short communication we describe the first probable case of acute hypocalcemia-related EPC. Eight months after a left parietal lobe cardioembolic stroke, a 74-year-old woman experienced a generalized tonic-clonic seizure for the first time in her life, at the beginning of a Clostridium difficile enterocolitis. Four days later, while the abdominal symptoms were clinically improving, continuous semi-rhythmic jerks of right face, shoulder and arm began suddenly. Despite several appropriated antiepileptic treatments those involuntary movements did not cease. On routine biochemical examination we noted a total calcium serum level of 1.2 mmol/L (normal range 2.1-2.8 mmol/L), not previously known. After intravenous calcium gluconate supplementation, the jerks started to fade, disappearing completely as a total calcium serum level of 1.9 mmol/L was reached. Two separated CT brain scans did not reveal new cerebral lesions. Neurophysiological studies did not show any cortical activity related to jerks. Taken together, the treatment refractoriness and the clinical improvement after ionic imbalance correction point towards a highly possible role of hypocalcemia in sustaining the activity of a previously silent epileptogenic focus.

Long-term evaluation of cognitive function and cerebral metabolism in liver transplanted patients.

INTRODUCTION: Patients with liver cirrhosis without overt hepatic encephalopathy (OHE) show alterations of cognitive function and metabolism which seem to not be fully reversible after liver transplantation (OLT), but the long-term outcomes have not be studied. METHODS: Fourteen cirrhotic subjects including alcoholic (n = 4), viral (n = 4), mixed (n = 5), and cholestatic (n = 2) without OHE were evaluated for OLT as well as 8 age-matched normal controls. All subjects underwent cerebral positron emission tomography (PET) with 18F-fluorodeoxyglucose to quantify cerebral glucose metabolism and neuropsychological evaluation to test memory, intelligence, and cerebral frontal functions. Transplanted patients underwent repeat evaluations at 1 and 10 years after liver transplantation. RESULTS: Compared with the controls patients with liver cirrhosis showed significantly reduced cerebral glucose metabolism in all cerebral cortical and subcortical regions. This observation correlated with the presence of alterations in neuropsychological tests evaluating memory, frontal tasks, and visuospatial memory. Among 12 patients who were transplanted, 10 underwent repeat neuropsychological evaluation at 1 year; in addition 5 underwent PET). At 10 years the 7 living patients had repeat neuropsychological evaluation. One year after OLT, transplanted patients showed significant amelioration of cerebral glucose metabolism in all cerebral regions with significant improvements in neuropsychological tests, despite 20% of patients showing residual defects in frontal tasks. The cognitive function did not further improve at 10 years after OLT. CONCLUSION: Patients with liver cirrhosis show altered cerebral function and metabolism that revert after successful liver transplantation, but with residual mild deficits in cerebral frontal functions, which seem to not improve in the long term.

Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.

Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.

Sudden, unexpected death due to undiagnosed frontal glioblastoma in a schizophrenic patient.

The incidence of sudden death due to undiagnosed primary intracranial tumor is low in forensic autopsy. We report a case of a 48-year-old white male, known to be a schizophrenic patient for several years, and in whom a medico-legal autopsy disclosed a large, previously undiagnosed, bilateral frontal glioblastoma infiltrating the genu of corpus callosum. We emphasize the importance of performing complete autopsy, including a thorough neuropathological examination, in all cases of sudden unexpected death, especially in those cases in which no extracerebral cause of death had been established and whose clinical history was primarily of a psychiatric nature.

Malignant transformation of a spinal cord ganglioglioma--case report and review of the literature.

Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have a benign clinical course. Rare cases display anaplastic features at the time of first presentation or progress to anaplastic gliomas over extended times. We report on a ganglioglioma of the spinal cord that recurred as a malignant glioma one and a half years after resection. The initial neoplasm was composed of a mixture of well-differentiated ganglionic and astrocytic cells. The recurrent tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial neoplasm was an abundance of small vessels with calcified walls, which mimicked a vascular malformation.

Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade.

Thiethylperazine (Torecan) is a piperazine phenothiazine employed to relieve vertigo. Its use may be associated with extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) (Sulkava, 1984), but parkinsonism has rarely been described. We describe a woman who, 1 month after the onset of thiethylperazine treatment, developed parkinsonism that disappeared 2 months after withdrawal of the drug. However, cerebral single-photon emission computed tomography (SPECT) with the dopamine (DA) D2 receptors ligand 123I-iodobenzamide (123I-IBZM) revealed a persistent reduced DA D2 receptors activity (by 45%) in the basal ganglia (BG), which may be clinically not effective.

Does liver-disease aetiology have a role in cerebral blood-flow alterations in liver cirrhosis?

BACKGROUND: Studies using brain-imaging techniques have shown changes in regional blood flow (rCBF) in patients with liver cirrhosis. It remains unknown whether the aetiology of liver disease accounts for these changes. AIMS: To evaluate whether the aetiology of liver cirrhosis is associated with different patterns of rCBF. MATERIALS AND METHODS: A total of 50 patients with end-stage liver disease and no overt encephalopathy were studied. Thirteen age-matched subjects admitted to the neurology department for headache were used as controls. Exclusion criteria were focal brain lesions, severe brain atrophy and any abnormalities found on computed tomography scan suggesting other central nervous system diseases, alcohol intake or use of neuroactive drugs for at least 6 months. rCBF was assessed using single-positron-emission tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (99mTc-HM-PAO) as a tracer in all patients and controls. The Mann-Whitney U test was used for statistical analysis. RESULTS: The liver-disease aetiology was as follows: alcoholic (A) in 19 patients; viral (V) (hepatitis B virus, hepatitis D virus, hepatitis C virus) in 14 patients; alcoholic with concomitant viral (A + V) in five patients; and cholestatic (C) (primary biliary cirrhosis, primary sclerosing cholangitis) in 12 patients. SPECT showed significantly lower rCBF in cirrhotic patients than in controls for most cortical and subcortical regions and in alcoholic and viral patients than in cholestatic liver disease patients for some cortical regions. When patients were grouped according to previous alcohol abuse (including cases with a concomitant viral aetiology), rCBF was significantly lower in the frontal superior, medial and temporal inferior regions in the alcoholic group. CONCLUSIONS: Cerebral blood flow is significantly lower in patients with liver cirrhosis than in controls and, among cirrhotics, it is lower in alcoholic and viral cirrhosis than in cholestatic liver disease. In patients with previous alcohol abuse, cerebral blood flow was significantly more reduced in the frontal and temporal regions compared with patients without previous alcohol abuse.

A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials.

In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmacology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.

Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14.

Detailed autopsy findings are reported for a patient with dopa-responsive dystonia genetically related to the dopa-responsive dystonia locus DYT14 on chromosome 14q13. Substantia nigra and locus ceruleus showed a normal abundance of severely hypomelanized dopaminergic neurons and no Lewy body. In the nigra, the reduction of melanin pigment was found to be asymmetric between the two sides and uneven within neurons, and the lateral aspect of the nigra appeared more affected than the medial, in a pattern similar to the neuronal loss in PD. Dopa-responsive dystonia has a unique neuropathologic signature that seems to be independent of its genotype.

Combined analysis of CSF betaA42 peptide and tau protein and serum antibodies to glycosaminoglycans in Alzheimer's disease: preliminary data.

Neuropathological hallmarks of Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles, containing betaA(42) peptide and tau protein, respectively. Amyloid plaques contain also glycosaminoglycans (GAGs). Whereas cerebrospinal fluid (CSF) levels of betaA(42) peptide and tau protein have been demonstrated as potential markers of Alzheimer's disease (AD), no data are available for GAGs. We determined (Elisa) tau and betaA(42) CSF levels, as well as serum antibodies to GAGs in 9 AD patients, and the values were analyzed in relation to age and severity of the disease. Beta-A42 and tau CSF levels were significantly reduced and increased, respectively, in AD patients when compared to controls, but they did not correlate with the severity of the disease. Despite their role in amyloidogenesis, we did not find evidence for the use of GAGs as diagnostic marker of AD.

[Transthoracic transvertebral approach for resection of an anteriorly located, calcified meningioma. Case report]. / Abord transthoracique transvertébral pour résection d'un méningiome calcifié de situation antérieure. A propos d'un cas.

We report the case of a 61-year-old woman, who developed progressive paraparesia over a period of 8 months. Conventional X-rays of the thoracic spine showed an intra-spinal calcified lesion at T10. On CT-scan and MRI, the lesion appeared anterior to the cord, thus making a posterior approach hazardous. Total resection of this calcified meningioma was achieved through a right transthoracic transcorporeal approach, under close monitoring of the somatosensory evoked potentials. Despite a delayed pseudomeningocele formation requiring an additional thoracotomy, outcome after 7 years is excellent with no residual neurological deficit. No recurrence was seen on a CT-scan performed two years after the surgery. Calcified anterior meningiomas of the spine are rare lesions. Surgical outcome has been unfavorable for a long time in relation with posterior or postero-lateral approaches. Although anterior transthoracic procedures are routinely performed for extradural spinal lesions, this approach is rarely used for intradural lesions. A calcified anterior spinal thoracic meningioma should be managed like the more frequent calcified thoracic disk hernia, despite the increased risk of cerebrospinal fluid effusion requiring subsequent repair.

Role of the distal balloon protection technique in the prevention of cerebral embolic events during carotid stent placement.

BACKGROUND AND PURPOSE: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. METHODS: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. RESULTS: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017). CONCLUSIONS: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.

Early fatal pontocerebellar hypoplasia in premature twin sisters.

We report clinical, neuroradiological and neuropathological findings of monozygotic twin sisters born at 30 weeks' gestation, with pontocerebellar hypoplasia (PCH) similar but not identical to type 2 PCH. They presented with hypertonia, jitteriness, spontaneous and provoked myoclonic jerks (hyperekplexia), apnoeic episodes, and progressive microcephaly. They died at 7 weeks of age from respiratory failure.

Effects of acute and chronic treatment with fluoxetine on regional glucose cerebral metabolism in rats: implications for clinical therapies.

The wide therapeutic spectrum of fluoxetine (e.g., antidepressant, antipanic, antiphobic, antiobsessive, analgesic, antimigraine) requires long-term administration and adaptive changes. To test whether adaptation involves the serotonin (5-HT) transporters, we measured the effects of fluoxetine on the regional cerebral metabolic rate for glucose (rCMRglc) in control rats or in rats pretreated for 2 weeks with fluoxetine (8 mg/kg, i.p., daily, 2 days wash out); rCMRglc was measured in 56 brain regions, using the quantitative [14C]deoxyglucose technique, at 30 min after i.p. administration of fluoxetine 0.4, 4 or 40 mg/kg, i.p., to non-pretreated rats or fluoxetine 4 mg/kg to pretreated rats. In non-pretreated rats, fluoxetine reduced rCMRglc in a dose-dependent fashion in 4 (7%, mean decrease 11%), 28 (50%, mean decrease 23%) and 37 (66%, mean decrease 32%) brain regions. In chronic fluoxetine-pretreated rats, fluoxetine decreased rCMRglc to a substantially lesser degree (eight regions, 14%; mean decrease, 10%). Subcortical brain regions (i.e., hypothalamic paraventricular, locus coeruleus and basal ganglia nuclei) that mediate the physiological responses to stress were very sensitive to fluoxetine acutely and subsensitive after chronic treatment. As kinetic tolerance to fluoxetine does not occur during chronic administration, the diminished rCMRglc responsivity to fluoxetine reflects dynamic, adaptive tolerance of 5-HT transporters and, consequently, increased synaptic 5-HT concentrations; the findings suggest that fluoxetine may be therapeutic by increasing the 5-HT-negative modulation upon areas that drive the abnormally hyperactive responses to stress found in several neuropsychiatric conditions.

Proximal myotonic myopathy: clinical, electrophysiological and pathological findings in a family.

Proximal myotonic myopathy (PROMM) is an autosomal dominant muscle disorder characterized by proximal weakness, myotonia, muscle pain and cataract. It resembles Steinert myotonic dystrophy (MD), but weakness is proximal, without facial muscle involvement, and the chromosome 19 CTG trinucleotide repeat expansion characteristic of MD is not present. We describe a further family with PROMM. Affected members complained of weakness of lower limbs or of myotonia. EMG revealed diffuse myotonic discharges. Muscle histology showed dystrophic abnormalities. The PROMM phenotype varies, even in the same pedigree, and may mimic MD or limb-girdle muscle dystrophy. EMG is particularly useful, since it may disclose myotonic discharges even in the absence of overt myotonia. Thus far it is not known whether PROMM is a single entity, or if it represents a heterogeneous group of disorders. This question will probably soon be settled through genetic analysis.