GianPietro Sechi

Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management.

Wernickes encephalopathy is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, the disorder is still greatly underdiagnosed in both adults and children. In this review, we provide an update on the factors and clinical settings that predispose to Wernickes encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis, we classify the common and rare symptoms at presentation and the late-stage symptoms. We emphasise the optimum dose of parenteral thiamine required for prophylaxis and treatment of Wernickes encephalopathy and prevention of Korsakoffs syndrome associated with alcohol misuse. A systematic approach helps to ensure that patients receive a prompt diagnosis and adequate treatment.

Reduced intravenous glutathione in the treatment of early parkinson's disease

1. Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinsons Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. This finding may indicate a means by which the nigra cells could be therapeutically supported. 2. The authors studied the effects of GSH in nine patients with early, untreated PD. GSH was administered intravenous, 600 mg twice daily, for 30 days, in an open label fashion. Then, the drug was discontinued and a follow-up examination carried-out at 1-month interval for 2-4 months. Thereafter, the patients were treated with carbidopa-levodopa. 3. The clinical disability was assessed by using two different rating scale and the Webster Step-Second Test at baseline and at 1-month interval for 4-6 months. All patients improved significantly after GSH therapy, with a 42% decline in disability. Once GSH was stopped the therapeutic effect lasted for 2-4 months. 4. Our data indicate that in untreated PD patients GSH has symptomatic efficacy and possibly retards the progression of the disease.

Multiple sclerosis–associated retrovirus (MSRV) in Sardinian MS patients

Abstract—Blood and CSF of Sardinian patients with MS and neurologic control subjects were tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at clinical onset, increasing with temporal disease progression, and 40% in control subjects. In blood, MSRV was detected in all MS patients, in most patients with inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may represent a marker of neurologic diseases of inflammatory origin.

Fatal hyperpyrexia after withdrawal of levodopa

We studied a patient affected with idiopathic Parkinsons disease and levodopa-induced dyskinesias. Fatal hyperpyrexia followed simultaneous levodopa withdrawal and a decrease in the dosage of diphenhydramine. The clinical features were those of the neuroleptic malignant syndrome. The rapid decrease in dopaminergic activity may have been important in causing the syndrome.

Treatment of cerebellar tremors with carbamazepine A controlled trial with long‐term follow‐up

We studied the effects of carbamazepine (CBZ) (400 and 600 mg per day) in 10 patients with cerebellar tremors in a single-blind manner. All patients improved on a clinical rating scale and by accelerometric recording; there was no improvement with placebo. Our data suggest that CBZ may be a valuable drug in cerebellar tremors.

The clinical spectrum of late-onset Alexander disease: a systematic literature review

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

Neurological disorders associated with Mycoplasma pneumoniae infection

Neurological syndromes caused by Mycoplasma pneumoniae (MP) infection are occasionally reported in adults, usually in the post‐infectious period, and three computed tomography documented cases have recently appeared in this journal. Here we present the cases of three young women with recent respiratory tract infection caused by MP some weeks prior to neurological complication documented by magnetic resonance imaging. Two cases suffered from demyelinating disorders of the central nervous system (CNS). The other case had a middle cerebral artery thrombosis, a rare complication of MP infection. Another potential risk factor for stroke in the latter case was the use of oral contraceptives. Recent infection with MP is discussed as a risk factor for cerebrovascular disorders and CNS demyelinating diseases.

Carbamazepine versus Diphenylhydantoin in the Treatment of Myotonia

A double-blind controlled trial was performed on 6 patients affected with Steinerts disease in order to evaluate the efficacy of two different dosages of diphenylhydantoin (PHT, 200 and 300 mg/day) and carbamazepine (CBZ, 600 and 800 mg/day) on the myotonic afterdischarge. Both dosages of PHT and CBZ induced a significant improvement of myotonia. For PHT a trend towards decreased efficacy is pointed out at toxic or at high dosages.

Risperidone, neuroleptic malignant syndrome and probable dementia with Lewy bodies.

1. Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro

The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to enhance the degradation of misfolded proteins, as in Alexanders disease. Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons in a rat model of Parkinsons disease was documented. However, which characteristics of ceftriaxone mediate its therapeutic effects remains unclear. Since, at the molecular level, neuronal α-synuclein inclusions and pathological α-synuclein transmission play a leading role in initiation of Parkinson-like neurodegeneration, we thought of investigating, by circular dichroism spectroscopy, the capability of ceftriaxone to interact with α-synuclein. We found that ceftriaxone binds with good affinity to α-synuclein and blocks its in vitro polymerization. Considering this finding, we also documented that ceftriaxone exerts neuroprotective action in an in vitro model of Parkinsons disease. Our data, in addition to the findings on neuroprotective activity of ceftriaxone on Parkinson-like neurodegeneration in vivo, indicates ceftriaxone as a potential agent in treatment of Parkinsons disease.