[The use of therapeutic apheresis in neurological diseases and comparison between plasma exchange and immunoadsorption]. / Utilizzo dell'aferesi terapeutica in corso di patologie neurologiche comparazione tra plasmaexchange ed immunoadsorbimento.

The use of plasmapheresis in neurological diseases with immune-mediated pathogenesis is widely certified. In recent years, the technological evolution of the dialysis membranes allowed to accompany the classical plasma exchange (PEX) treatment of apheresis by means of selective adsorption (IA). It has proved to be of equal therapeutic efficacy and, at the same time, devoid of most of the PEX side effects. The recent guidelines of the American Society for Apheresis (ASFA) and, later, the American Academy of Neurology, outlined directions and diagrams for the application of the method that has found wide use in many neurological diseases on the basis of auto-antibodies; in particular in Myasthenia Gravis, Guillain-Barre Syndrome, Multiple Sclerosis and Chronic Demyelinating Polyradiculoneuropathy. We add our experience in the treatment of 13 patients suffering from Myasthenia Gravis, treated over a four years period with filters containing tryptophan immunoadsorption in polyvinyl alcohol gel. The results confirm the achievement of a rapid regression of clinical symptoms, together with the rapid fall in the levels of antibody against acetylcholine-receptor. Therefore, the method of AI is to be considered of equal therapeutic efficacy of PEX, providing greater security in its use.

PON1 activity and genotype in patients with arterial ischemic stroke and in healthy individuals.

OBJECTIVE: Paraoxonase-1 (PON1) is an esterase with antioxidant properties. Low PON1 enzyme activity or specific allelic polymorphisms seem to be associated with the risk of developing coronary artery disease or acute ischemic stroke (AIS). Our objective was to determine the distribution of both PON1 enzyme activity and its genotype in a group of patients with AIS. MATERIALS AND METHODS: PON1 activity and the relative Q192R and L55M polymorphisms in the PON1 gene were assessed on 126 survivors of a first AIS and in 92 healthy subjects. RESULTS: The genotype distribution for PON1 Q192R and L55M polymorphisms was similar in AIS patients and healthy subjects, but patients carrying the QRLL or RRLL genotype combination had lower PON1 enzyme activity compared with healthy subjects with the same genotype. CONCLUSION: We postulate that lower than expected PON1 enzyme activity within specific genotypes might explain the reported association between R and L alleles and the risk of developing AIS.

Serum levels of carbamazepine and cortical excitability by magnetic brain stimulation.

We investigated the correlation between serum levels of carbamazepine (CBZ) and motor excitability studied by different parameters of transcranial magnetic stimulation (TMS) in patients at the beginning of antiepileptic treatment. A total of 10 patients with complex partial seizures following stroke were treated with loading doses of CBZ. Motor evoked potential (MEP) was recorded from the thenar eminence (TE) muscles of the unaffected arm. In all patients, we studied rest and active motor threshold (rMT, aMT), MEP amplitude and cortical silent period (CSP). In three patients, intracortical inhibition (ICI) and intracortical facilitation (ICF) were measured using paired TMS at short interstimulus intervals (1-25 ms). The recording sessions were performed before treatment and after 7, 15 and 60 days (SD=16 days). Serum level of CBZ were monitored at each recording session. We observed a progressive increase in rMT and aMT until the serum levels of CBZ reached a steady state condition. No significant changes were observed in MEP amplitude, CSP, ICI and ICF. This study documents the increase of both motor threshold and drug serum levels in patients treated with loading doses of CBZ, suggesting a relationship between drug metabolism and the effect on motor cortical excitability.

Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease characterized by recurrent sensory or motor manifestations. The molecular basis of HNPP is a deletion on chromosome 17p11.2. We studied a family (father, 61 years; mother, 55 years; 6 children of mean age 25.3 years) showing symptoms of carpal tunnel syndrome in 4 members (the parents and 2 sons). No one of them reported episodes of nerve palsy. In all the patients, except the mother and the younger son, electrophysiologic evaluation showed a sensorimotor polyneuropathy with delayed sensorimotor latencies. Genetic analysis was carried out in the parents and the eldest son. The 17p11.2 deletion was detected in the father and son, indicating paternal transmission of the disease. Clinical manifestations of HNPP may be atypical. Sometimes there is no history of acute nerve palsy, as in this family. For this reason, the frequence of HNPP might be underestimated. Electrophysiological examination is of great importance for the diagnosis of HNPP. Genetic analysis is a rapid and reliable diagnostic tool that can be combined with simplified electrophysiological examination, avoiding the need for nerve biopsy. In conclusion, the diagnosis of HNPP should be invoked in early onset entrapment neuropathies.

Multiple radiculopathy of the lower limbs in a cancer patient with meningeal carcinomatosis.

Meningeal carcinomatosis occurs in 1%-5% of patients with breast cancer. Early diagnosis and aggressive treatment of neurologic involvement are important factors of prognosis. We report a case of a 52-year-old woman who was affected by bilateral breast carcinoma treated with surgery and chemotherapy. Six years after she had become asymptomatic, X-rays showed lumbar spine metastases which were treated with radiotherapy. After 1 year she began to suffer from lower limb paresthesias, unsteadiness and unstable gait. Clinical examination showed lower limb sensory ataxia with lack of knee and ankle reflexes, and hypopallesthesia from the iliac spine to the foot. Spinal magnetic resonance imaging (MRI) with contrast agent revealed no medullar compression. Electromyography disclosed bilateral involvement of L4-L5-S1 roots and corresponding paraspinal muscles. Sensory and motor conductions were normal. Cerebrospinal fluid (CSF) examination showed the presence of neoplastic cells, confirming the diagnosis of meningeal carcinomatosis. Our patient underwent 9 cycles of intrathecal methotrexate therapy (25 mg/cycle) with improvement of ataxia and relief of paresthesias. One year later, CSF examination is still negative. We point out the importance of electrodiagnostic studies and CSF examination in the early documentation of root involvement in cancer patients, when computed tomography, MRI and myelography are normal. Early diagnosis may lead to effective therapy which prolongs survival.

Adult onset Krabbe's leukodystrophy: a report of 2 cases.

Krabbe's disease with adult onset is rare; neurological symptoms begin in childhood or at a juvenile age. Two brothers with adult onset of the disease are here reported; 1 sibling developed parapareto-ataxic gait while the other was asymptomatic. Magnetic resonance imaging showed areas of demyelination in the white matter of the brain, while nerve conduction was completely normal. In both patients deficiency of galactosylceramide beta-galactosidase was comparable to the infantile form.

Neurophysiological study of Horner's syndrome.

Sympathetic skin response from the forehead and from the hand obtained by using electric, acoustic stimuli and during deep breathing was recorded in normal subjects and in patients suffering from Horner's syndrome in order to characterize this clinical picture neurophysiologically. The reliability of the method points to its possible usefulness in the pre-postganglionic differential diagnosis also.