Rosaria Plasmati

Transcranial magnetic stimulation in epileptic patients Usefulness and safety

We studied 58 patients with partial or generalized epilepsy who had transcranial magnetic stimulation (TMS) of the brain motor regions. Short-term monitoring disclosed that the stimulation did not provoke seizures or EEG changes in any patient. Long-term follow-up disclosed that the epileptic condition was not made worse by TMS. TMS, as currently used for monitoring conduction in central motor pathways, does not induce seizures in drug-treated epileptic patients.

Brain white matter damage in SCA1 and SCA2. An in vivo study using voxel-based morphometry, histogram analysis of mean diffusivity and tract-based spatial statistics

BACKGROUND AND PURPOSE Neurodegeneration in spinocerebellar ataxia type 1(SCA1) and 2(SCA2) is associated with white matter(WM) damage. Voxel-Based Morphometry(VBM), histogram analysis of mean diffusivity(MD) and Tract-Based Spatial Statistics(TBSS) enable an in vivo quantitative analysis of WM volume and structure. We assessed with these 3 techniques the whole brain WM damage in SCA1 and SCA2. PATIENTS AND METHODS Ten patients with SCA1, 10 patients with SCA2 and 10 controls underwent MRI with acquisition of T1-weighted and diffusion tensor images. The results were correlated with severity of clinical deficit. RESULTS VBM showed atrophy of the brainstem and cerebellar WM without significant differences between SCA1 and SCA2. Focal atrophy of the cerebral subcortical WM was also present. Histogram analysis revealed increased MD in the brainstem and cerebellum in patients with SCA1 and SCA2 which in SCA2 was more pronounced and combined with mild increase of the MD in the cerebral hemispheres in SCA2. In SCA1 and SCA2 TBSS revealed decreased fractional anisotropy(FA) in the inferior, middle and superior cerebellar peduncles, pontine transverse fibres, medial and lateral lemnisci, spinothalamic tracts, corticospinal tracts and corpus callosum. The extent of tract changes was greater in SCA2 patients who also showed decreased FA in the short intracerebellar tracts. In both diseases VBM, histogram and TBSS results correlated with clinical severity. CONCLUSIONS Brain WM damage featuring a pontocerebeellar atrophy is similar in SCA1 and SCA2 but more pronounced in SCA2. In both diseases it correlates with severity of the clinical deficit.

Transthyretin amyloidosis and superficial siderosis of the CNS

OBJECTIVE To describe a previously unreported clinical and radiologic presentation of hereditary transthyretin (TTR)-related amyloidosis. BACKGROUND Unexplained cerebellar ataxia, pyramidal syndrome, and hearing loss are observed in some patients with TTR-related amyloidoses. METHODS We performed clinical, radiologic, and pathologic examinations of three family members with TTR-related (Ala36Pro) amyloidosis. RESULTS The patient was a 69-year-old woman with vitreal amyloid deposits, progressive sensorineural deafness, cerebellar ataxia, pyramidal syndrome, and recurrent transient neurologic symptoms. Cranial MRI showed symmetric thin rims of low signal intensity in T2- and T2*-weighted images in the cortex of the sylvian fissures, of the cerebellar hemispheres and vermis, and in the quadrigeminal plate consistent with superficial siderosis of the CNS. Her older daughter had vitreal amyloid deposits, acute Brown-Sequard syndrome at C4, acute sensorineural deafness, and recurrent transient neurologic symptoms. Cranial MRI at age 48 revealed a rim of low signal intensity in T2- and T2*-weighted images in the superior vermis folia and the right sylvian cortex. In addition, two small hemosiderin deposits were seen in the left parietal cortex. Lumbar puncture yielded colorless CSF with increased ferritin content and was followed by fourth ventricle hemorrhage. Cranial MRI 11 months later showed progression of brain hemosiderin deposits. The younger daughter had vitreal deposits, sensorimotor polyneuropathy, and acute sensorineural hearing but no evidence of siderosis on cranial MRI. She died at age 43 years of posterior fossa subarachnoid hemorrhage, and the neuropathologic examination showed amyloid deposition in the leptomeningeal spaces and vessels. CONCLUSION Transthyretin-related amyloidosis may cause superficial siderosis of the CNS through subarachnoid bleeding related to meningovascular amyloid deposition.

Transient global amnesia as a postictal state from recurrent partial seizures

Summary: A 60‐year‐old patient had a 3‐year history of recurrent memory disturbances. The video electroen‐cephalographic (EEG) recording of one attack showed that the amnesic state, which clinically resembled transient global amnesia, was characterized by a normal EEG tracing followed by electroclinical complex partial seizures. We suggest that “epileptic” transient global amnesia is postictal in nature.

Hypertension, hyperekplexia, and pyramidal paresis due to vascular compression of the medulla

Article abstract MRI showed impingement of the vertebral artery on the left lateral medulla in two patients with arterial hypertension, exaggerated startle reflexes (hyperekplexia), and progressive spastic paresis. One patient underwent microvascular decompression with normalization of arterial hypertension, disappearance of hyperekplexia, and improvement of spastic paresis. The combination of arterial hypertension, hyperekplexia, and progressive spastic paresis should arouse suspicion of neurovascular compression of the lateral medulla.

Genotypic and phenotypic correlation in an Italian population of hereditary amyloidosis TTR-related (HA-TTR): clinical and neurophysiological aids to diagnosis and some reflections on misdiagnosis

131 HA-TTR patients from a single referral centre presented at onset five major clinical syndromes: (1) the typical “Portuguese variant” axonal polyneuropathy with dissociated (syringomyelic like) sensory loss and autonomic dysfunction; (2) bilateral carpal tunnel syndrome; (3) restless leg syndrome with impotence and unexplained loss of weight; (4) pure motor neuropathy without autonomic abnormalities; (5) recurrent small brain or spinal cord ischemia or haemorrhages with leptomeningeal amyloid deposition (and late superficial siderosis of the central nervous system) and vitreous deposits. Some patients in our population presented a “pseudodemyelinating” onset of the somatic neuropathy, as well as atypical motor neuropathy simulating lower motor neuron disease. The five syndromes can overlap in advanced stages of the disease. Genetic screening of HA-TTR could be worthwhile in any idiopathic progressive axonal peripheral neuropathy, as well as in drug resistant demyelinating sensory-motor neuropathy or in pure motor neuropathy, when multi-organ involvement is present.

Mild Lafora disease: Clinical, neurophysiologic, and genetic findings

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty‐three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow‐up duration was 13.2 ± 8.0 years. NHLRC1 mutations were detected in 18 patients; EPM2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as “mild” and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography (EEG) and giant somatosensory evoked potentials, as compared to patients with typical LD. However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD. The occurrence of specific NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.

Familial amyloidotic polyneuropathy: transthyretin (prealbumin) variants in kindreds of Italian origin

SummaryAs part of an epidemiological study that aims to characterize chemically the mutation(s) in transthyretin (TTR) related to familial amyloidotic polyneuropathy (FAP) of different ethnic origins, studies were carried out on TTR from two FAP kindreds of Italian origin. Two different criteria were employed in the characterization of TTR from these kindreds: (1) immunoblotting of cyanogen bromide fragments for screening of TTR(Met30) and (2) isoelectric focusing. TTR(Met30) was not detected but other substitutions were demonstrated using isoelectric focusing techniques. One of the variants found is a basic TTR variant. The substitutions occurring in the variant TTRs of these two kindreds are not known and are presently under study.

Trigeminal neuralgia associated with contralateral intracranial tumour: a false localising sign caused by vascular compression? Report of two cases.

I Bots GTAM, Wattendorff AR, Burma OJS, Roos RAC, Endtz LJ. Acute myelopathy caused by fibrocartilaginous emboli. Neurology 1981;31:1250-6. 2. Hubert JP, Ectors M, Ketelbant-Balassee P, Flament-Durant J. Fibrocartilaginous venous and arterial emboli from the nucleus pulposus in the anterior spinal system. Eur Neurol 1974;11:164-71. 3 Srigley JR, Lambert CD, Bilbao JM, Pritzker KPH. Spinal cord infarction secondary to intervertebral disc embolism. Ann Neurol 1981;9:296-300.

A novel T137A SOD1 mutation in an Italian family with two subjects affected by amyotrophic lateral sclerosis

Abstract Mutations in the superoxide dismutase-1 (SOD1) gene occur in some forms of familial amyotrophic lateral sclerosis (ALS). To date about 150 mutations are known to involve this gene. Here we describe a novel missense mutation in exon 5 of the SOD1 gene in an Italian family with two members affected by ALS. Sequencing of the SOD1 gene was performed on 11 members of the family and 75 healthy controls. Electron microscopy was also performed on one ALS patient. We identified a heterozygous mutation in codon 137 leading to substitution of threonine by alanine. Further studies are needed to clarify the role of this alteration in ALS aetiopathogensis; nevertheless, T137A seems to represent a new missense mutation of the SOD1 gene in ALS patients.