Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

BACKGROUND AND PURPOSE: Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. RESULTS: Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su93-108 and HERV-W env-su248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. CONCLUSIONS: Increased circulating levels of Abs directed against the HERV-W env-su93-108 and HERV-W env-su248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS.

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.

Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls.

Chlamydia pneumoniae infection is a common event in neurological patients and recovery of C. pneumoniae DNA in the cerebrospinal fluids (CSF) of multiple sclerosis (MS) patients could represent an epiphenomenon. We assessed the relevance of C. pneumoniae infection in 62 CSF samples from 32 MS patients and 30 neurological controls by means of PCR, immunofluorescence microscopy, enzyme-linked fluorescence and antibody detection. Multiple sclerosis (9.3%) and neurological controls (13.3) had similar percentage of anti-C. pneumoniae antibodies. However, C. pneumoniae DNA was only detectable in MS patients' CSF (9.3%). Our data support the hypothesis that C. pneumoniae persistence in some MS patients may be the result of an impaired clearance within the central nervous system.

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.

Co-variation of free amino acids in brain interstitial fluid during pentylenetetrazole-induced convulsive status epilepticus.

Effects of pentylenetetrazole (PTZ)-induced convulsive status epilepticus on free amino acids changes in venous blood, CSF and interstitial fluid (IF) of the brain were examined in dogs. A volume of brain IF sufficient for analysis was obtained by chronically implanted tissue cages. The onset of PTZ-induced convulsive seizures seemed mainly related to a marked increase of glutamate, aspartate, taurine, glycine and phosphoserine while, the maintenance and frequency of seizures seemed related to a marked increase of serine and glycine, in combination with a moderate rise of glutamate. L-alpha-Aminoadipate was recovered in moderate amount in epileptic brain IF, while, in controls, this compound was present in minimal amount. The observed complex temporal variation of the amino acidic pattern may play a role in PTZ-induced seizures and, possibly, in pharmacological kindling and brain structural alterations induced by PTZ.

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 Parkinson's 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.

Acute hyponatremia and neuroleptic malignant syndrome in Parkinson's disease.

1. The neuroleptic malignant syndrome (NMS) may occur, occasionally, in Parkinson's disease (PD) after withdrawal of antiparkinsonian drugs. However, the circumstances in which the NMS occurs and the pathophysiologic mechanisms remain uncertain. 2. The authors studied a woman with PD, who developed hyperthermia, increased muscular tone, tremor, signs of autonomic dysfunction and stupor as symptoms of acute hyponatremia due to gastrointestinal loss of sodium in excess of water. 3. The correction of hyponatremia led to a complete recovery after about 6 hours. During this period the antiparkinsonian therapy was not modified. 4. An acute imbalance of sodium in the central nervous system may play a role in the pathophysiology of NMS.

Cerebral and cerebellar diaschisis following carbamazepine therapy.

1. The regional cerebral blood flow was studied by SPECT in patients with partial epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2. Both a qualitative visual interpretation and a semiquantitative analysis of SPECT was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ serum concentrations were assayed. 3. After therapy, in three patients with focal epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with respect to the side of the epileptic focus in the opposite hemisphere. No morphologic changes were detected at MRI in the cerebral or cerebellar remote hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the corticopontocerebellar pathways and on the corticocallosal connections.

Brain interstitial fluid collected through implanted tissue cages.

The physicochemical properties of the whole-brain interstitial fluid (IF) are unknown. A volume of whole-brain IF sufficient for analysis was obtained through a small, hollow, multiperforated polypropylene sphere implanted for 4-5 weeks into the dog brain parenchyma. The main physicochemical properties of the whole-brain IF were characterized, in comparison with the physicochemical properties of cerebrospinal fluid and blood/serum.