Alberto Primavera

Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau.

The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.

Mycophenolate mofetil in dysimmune neuropathies: A preliminary study

Mycophenolate mofetil (MM) is an immunosuppressant that has been used successfully for preventing the rejection of renal, heart, or liver transplants and for the therapy of immune-mediated diseases.4 It shows modest side effects and has a lower risk for late malignancies compared with other immunosuppressive drugs.1 Recently, MM has been used also for the treatment of myasthenia gravis, polymyositis, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and multifocal motor neuropathy (MMN).2,7,10 We treated four patients with possible, probable, or definite MMN11 and two with CIDP8 (Table 1) who were on large doses of intravenous immunoglobulins (IVIg), with the hope of reducing or withdrawing IVIg while maintaining a satisfactory and stable clinical state. Four patients were also receiving other immunomodulating agents. Patients received oral MM in a dosage of 1 g twice daily, for an average of 9 months (range, 6–12 months). Prior to MM treatment, all patients underwent several attempts to reduce IVIg dosage, resulting in clinical worsening, even in subjects receiving other immunomodulating agents. Patients were evaluated at baseline and each month thereafter, using the Medical Research Council (MRC) sumscore6 and the Immune Neuropathy Course and Treatment (INCAT) arm and leg disability scores.5 The values of the INCAT scale at baseline ranged from 0 to 3 (mean, 1.5). Full blood count, renal and liver function, and serum amylase levels were monitored every 2 months. Side effects were recorded and graded according to the Common Terminology Criteria for Adverse Events.9 All the patients provided informed consent to participate in the study. Table 1 summarizes the details of each patient. In five patients we did not observe any worsening in MRC sumscore or INCAT disability scale despite a significant reduction in IVIg dosage. On average, before starting MM treatment patients received 2g/kg every 4 weeks. After 6 months the mean dosage of IVIg was 0.75 g/kg every 4 weeks. In patients 1 and 2, IVIg infusion was reduced by 50% after 2 months and discontinued after 4 months. After 1 year of therapy with MM, IVIg treatment remains discontinued. In patient 4, the addition of MM allowed a reduction in IVIg dose to 50% after 4 months. In patient 3, IVIg dose was reduced by 25% but only for 4 months; symptoms relapse then required a return to the previous IVIg schedule. In patients 5 and 6, who had CIDP, IVIg dosage was reduced by 50%. After follow-up ranging from 6 to 12 months there was no deterioration in the MRC sumscore or in the INCAT disability scale in patients 1, 2, 4, 5, and 6; indeed, in patients 1 and 2 we observed a minimal improvement of overall disability within 2 months of starting MM. Finally, azathioprine (patients 3, 5, and 6) and cyclophosphamide (patient 2) were discontinued after 3 months of combined IVIg and MM treatment. Patients 1 and 4 discontinued MM because of loss of appetite, weight loss, abdominal pain, and increase of amylase levels (grade 1 in both cases). Patient 5 developed mild leukopenia (grade 1). Recently, MM has been introduced for the treatment of immune-mediated neuromuscular disorders,2,3 but the findings in only one patient with MMN and nine patients with CIDP have been published, to our knowledge, with conflicting results.7,10 We found that MM, in patients with MMN and CIDP, is effective in reducing IVIg requirement and in replacing other, more toxic, drugs. Only one patient with MMN relapsed, after 4 months, perhaps because of longer duration of disease, as previously observed in another series of patients.10 In fact, axonal impairment, more than immune-mediated de-

Wernicke-Korsakoff Encephalopathy Following Biliopancreatic Diversion

Wernicke-Korsakoff disease with sensory-motor neuropathy was diagnosed in three out of a series of 1663 patients (0.18%), with onset 2, 3 and 5 months after biliopancreatic diversion. Precipitating factors were vomiting, minimal food intake, anorexia, rapid weight loss, and glucose-containing intravenous feeding. Recovery was partial in two and complete in one of the patients. In the early postop, prophylactic thiamine should be given to the patients with excessively limited eating capacity. Larger doses of thiamine should be instituted parenterally either in the case of suspected Wernicke-Korsakoff encephalopathy or before starting feeding for protein malnutrition.

Prognosis of transient global amnesia: a long-term follow-up study.

A long-term follow-up study was performed on patients with transient global amnesia (TGA) in order to evaluate the prognosis, the recurrence rate and the occurrence of stroke and dementia. 102 patients (57 women, 45 men; mean age 62.8 +/- 9.4 years) were prospectively included and followed up. The follow-up duration ranged between 12 and 241 months with an average value of 82.2 +/- 51.1 (mean +/- SD). The death rate showed no difference from that of sex- and age-matched subjects. TGA recurred in 19 cases (18.63%). Only 4 patients suffered subsequent stroke, and only 3 showed intellectual deterioration. TGA prognosis was shown to be better than that of RIA and lacunar patients.

Clarithromycin-induced neurotoxicity in adults

Clarithromycin is a relatively new antibiotic of the macrolide family heralded for an improved side effect profile, dosing schedule, and microbiological activity relative to its parent compound, erythromycin. We review the literature on clarithromycin-induced neurotoxicity in adults and present an illustrative case. A total of 38 patients with clarithromycin-induced neurotoxicity have been reported. The average age of patients was 51.3 years (range: 19-87 years) with females comprising 52.6% of patients. Psychiatric illness was the most common comorbidity, while only two patients had renal failure. Clarithromycin had been prescribed for respiratory infections in most patients, and only two patients were receiving more than 1000 mg/day of antibiotic. The symptoms started 1 day to 10 days after starting clarithromycin (mean: 5 days). A total of 71% of patients were under treatment with concomitant medication, and eight patients were undergoing treatment with psychoactive drugs. Patients had a very good outcome after clarithromycin was discontinued, but medication with neuroleptics or benzodiazepine was required for 58% of patients in the acute phase. Only four patients underwent an electroencephalogram (EEG). Our illustrative patient was a 74-year-old woman with clarithromycin-induced delirium due to non-convulsive status epilepticus (NCSE). Her clinical symptoms and electroencephalogram (EEG) readings dramatically improved after discontinuation of clarithromycin. The mechanism underlying the central nervous system side effects remains unclear. We suggest including an EEG in the diagnostic procedures of patients under treatment with clarithromycin who develop features of neurotoxicity because an EEG can help to differentiate patients with psychiatric illness from those with encephalopathy or epilepsy. Because of the widespread use of clarithromycin, clinicians should be aware of its neurotoxicity. Early detection of clarithromycin-induced neurotoxicity and discontinuation of the drug may result in full recovery.

Correlation between Mini-Mental State Examination and Quantitative Electroencephalography in Senile Dementia of Alzheimer Type

The quantified electroencephalogram (qEEG) of patients with senile dementia of the Alzheimer type (SDAT) and normal elderly subjects was related to the Mini-Mental State (MMS) score. A statistically significant correlation was observed between MMS score and some qEEG parameters. This correlation indicates that the use of adequate spectral parameters of qEEG may provide information on the cognitive impairment of elderly subjects and may reduce the false-positive rate at a neuropsychological examination.

Nonconvulsive Status epilepticus during Cephalosporin Therapy

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.

Quantitative Electroencephalography in Parkinson’s Disease, Dementia, Depression and Normal Aging

The relationship between depression and dementia in Parkinsons disease (PD) has rarely been explored. Using a quantitative EEG (qEEG) parameter, we studied four groups of subjects: PD, demented Alzheimers type and major depressed patients and normal controls. The qEEG data were compared with those of the Mini-Mental State and the Hamilton Depression Scale. The qEEG pattern was different in the four groups of subjects. Moreover, there was a significant correlation between the qEEG data and the other variables, and, particularly, with the cognitive performances. Our findings demonstrate that the qEEG method of assessment may give valuable data for a better classification of dementia syndromes and for a distinction between dementia and pseudodementia.

Lacunae and Cribriform Cavities of the Brain

Fifty-one brains showing lacunae and 30 with cribriform cavities have been identified out of 191 examined brains. A histologic and immunohistochemical study with the peroxidase-antiperoxidase method for glial fibrillary acidic protein has been carried out in selected cases. The number, site, associated arterial lesions and the microscopic appearance of lacunae and cribriform cavities are reported. Lacunae are small cavities usually, but not always due to softenings; cribriform cavities are dilatations of the perivascular space. Two types of cribriform cavities have been identified, according to the histological appearance of the surrounding tissue: type 1 with normal and type 2 with rarefied and abnormally gliotic surrounding nervous tissue. Sixteen cases showing a cribriform state in the basal ganglia exhibited a pseudobulbar palsy or extrapyramidal rigidity. Pseudobulbar palsy of striate form or parkinsonism may be ascertained in some cases only by histological and immunohistochemical examination.

De novo status epilepticus as the presenting sign of neurosyphilis.

Summary: Although the incidence of seizures in neurosyphilis ranges from 14 to 60%, status epilepticus (SE) as a presenting complaint of neurosyphilis is definitely rare. A 44‐year‐old human immunodeficiency virus (H1V)‐negative man with no history of epilepsy suddenly presented with acute mental confusion and was diagnosed as having a de novo complex partial nonconvulsive SE. Cerebrospinal fluid (CSF) findings, neuroimaging, and clinical course indicated that SE was the presenting symptom of an undiagnosed syphilitic meningovasculitis. The case is presented with a review of previous reports to emphasize the differential features and to underscore the importance of considering neurosyphilis among the possible causes of de novo SE.