Felix Benninger

Update on herpes virus infections of the nervous system.

Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) are human neurotropic viruses that establish latent infection in dorsal root ganglia (DRG) for the entire life of the host. From the DRG they can reactivate to cause human morbidity and mortality. Although they vary, in part, in the clinical disorders they cause, and in their molecular structure, they share several features that govern the biology of their infection of the human nervous system. HSV-1 is the causative agent of encephalitis, corneal blindness, and several peripheral nervous system disorders; HSV-2 is responsible for meningoencephalitis in neonates and meningitis in adults. The biology of their ability to establish latency, maintain it for the entire life of the host, reactivate, and cause primary and recurrent disease is being studied in animal models and in humans. This review covers recent advances in understanding the biology and pathogenesis of HSV-related disease.

Toll-like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE-induced epilepsy in mice.

Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll‐like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE).

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties

To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever.

Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury.

Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury.

Seizures as presenting and prominent symptom in chorea-acanthocytosis with c.2343del VPS13A gene mutation.

The aim of the study was to characterize the clinical features of nine patients in three families with chorea‐acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene.

Nocturnal carbon dioxide monitoring in patients with idiopathic intracranial hypertension.

BACKGROUND Idiopathic intracranial hypertension may be associated with sleep apnea. This study evaluated the incidence of sleep breathing disorders in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS Overnight respiratory monitoring was performed in 22 untreated patients with idiopathic intracranial pressure diagnosed at a tertiary medical center over a two-year period and 12 sex- and age-matched control subjects. Breathing measures included heart rate, respiratory rate,oxygen saturation, and continuous end-tidal capnography. Sleep quality and daily fatigue were assessed by self-report questionnaires. RESULTS Mean age of the study group was 32.6±12.2 years and of the control group, 37.0±12.9 years. Neither group had significant findings of hypoxia or hypercarbia during sleep, and there were no between-group differences in mean carbon dioxide level (patients, 35.8±4.41 mmHg; controls, 37.6±4.38 mmHg; p>0.02) or minimal oxygen saturation (96.35±1.99% and 5.69±1.71%, respectively; p>0.02). The study group had significantly more events of apnea (CO2) per hour of sleep than the control group (1.21±1.38 and 0.92±0.56, respectively; p=0.02), although values were still within normal range (<5/hr). CONCLUSION Idiopathic intracranial hypertension is not associated with a clinically significant nocturnal breathing abnormality, and hypercarbia is apparently not involved in the pathogenesis. However, it is possible that a subtle increase in paroxysmal sleep apnea (CO2) events might be sufficient to cause vasodilatation of the cerebral blood vessels, thereby increasing intracranial pressure. Screening for sleep apnea may be appropriate in idiopathic intracranial hypertension patients, and further studies are needed to clarify this issue.

Atypical case of Morvan's syndrome.

Morvans syndrome is a rare neurological condition characterized by the combination of neuromyotonia, autonomic instability and encephalopathy, associated with auto-antibodies against voltage-gated potassium channels. We report a patient with an initial presentation suggestive of typical Guillain-Barré syndrome (GBS), who later developed clinical and laboratory features compatible with Morvans syndrome. Several months after resolution of the neurological symptoms, as well as disappearance of the characteristic anti-leucine-rich, glioma inactivated 1 (anti-LGI1) antibodies, the patient presented with episodes of fever of unknown origin, during which the antibodies became positive again, suggesting the possibility of a relapse. In this case, both the GBS-like symptoms at presentation and the isolated episodes of fever of unknown origin during follow-up are atypical, and may suggest the presence of an additional, yet unknown antibody.

Steroids in bacterial meningitis: yes

Bacterial meningitis is an infectious condition associated with severe morbidity and mortality, even with rapid diagnosis and appropriate antibiotic therapy. Despite decrease in the rate of bacterial meningitis brought about by vaccination programs against Haemophilus influenzae type-B and Streptococcus pneumonia, the incidence of meningitis is still unacceptably high and acute treatment remains the mainstay of therapy. The infection is accompanied by intense inflammatory response, which may carry deleterious effects upon the tissue. This led to the possibility of adjuvant corticosteroid therapy, as an anti-inflammatory agent, in bacterial meningitis. The debate focuses on the rational and evidence supporting and refuting such an approach.

Maraviroc in PML-IRIS A separate ball game under HIV infection and natalizumab?

Progressive multifocal leukoencephalpathy (PML) is a severe, often fatal, opportunistic infection of the CNS. First reported in 1958 as a white matter disorder in 3 patients with lymphoproliferative disorders,1 subsequent studies revealed a polyomavirus, named John Cunningham (JC) virus from the initials of the patient from whose brain it was initially isolated, as the causative agent. Despite previous reports, there is no evidence that PML is caused by either SV40 or BK virus.2

Psychiatric side effects of acute high-dose corticosteroid therapy in neurological conditions.

It has been implied that high-dose corticosteroids (CSs) commonly cause psychiatric side effects. Here, we examined the rate and risk factors of psychiatric side effects during high-dose CS treatment in patients with neurological disorders. Patients treated with high-dose intravenous CSs for neurological disorders were evaluated for depression, mania, and psychosis using the Beck Depression Inventory, the Geriatric Depression Scale, the Young Mania Rating Scale, and the Brief Psychiatric Rating Scale before CS treatment, immediately after, and 1 month following treatment. Forty-nine consecutive patients were monitored. There was a reduction in the Beck Depression Inventory and Geriatric Depression Scale scores as well as in the Brief Psychiatric Rating Scale scores throughout the study period and a transitory increase in the Young Mania Rating Scale score immediately after CS administration. Thus, a tendency to develop transient mild euphoria during high-dose CS treatment exists, but is reversible at 1 month, whereas a reduction in depressive symptoms tended to persist. Overall, our data indicate that high-dose CS treatment for neurological diseases is relatively safe with respect to psychiatric complications.