Upper motor neuron involvement in X-linked recessive bulbospinal muscular atrophy.

OBJECTIVE: Clinicopathological findings of X-linked recessive bulbospinal muscular atrophy (SBMA) are indicative of lower motor neuron and primary sensory neuron involvement. The aim of our study was to investigate the presence of subclinical upper motor neuron (UMN) dysfunction in this disease. METHODS: Two siblings with clinical presentation, routine electrophysiological tests, histopathological features of muscle and nerve biopsies and genetic testing consistent with diagnosis of SBMA underwent transcranial magnetic stimulation (TMS). The analysed parameters were motor evoked potential (MEP) threshold, silent period (SP) and central motor conduction time. Intracortical inhibition with paired pulses from 1 to 6ms interstimulus intervals (ISIs) was evaluated in the older brother. RESULTS: MEP parameters were significantly altered in limb and cranial muscles and MEP suppression after paired stimulation significantly reduced in the older brother. MEP abnormalities were present in one lower limb, but SP abolished in all limbs, in the younger brother. CONCLUSIONS: Subclinical involvement of UMNs may be present in patients affected by SBMA. This finding suggests that the array of neuronal systems whose function may be affected by the pathogenic process of SBMA is larger than it was considered so far. SIGNIFICANCE: TMS is a sensitive diagnostic tool for the identification of UMN dysfunction and should be included in the diagnostic evaluation of patients with SBMA.

Validation of the nerve axon reflex for the assessment of small nerve fibre dysfunction.

OBJECTIVE: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. METHODS: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. RESULTS: Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p<0.0001), NDS (r(s) = -0.665; p<0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response <50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. CONCLUSION: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy.

Subacute demyelinating polyneuropathy in B-cell lymphoma with IgM antibodies against glycolipid GD1b.

Peripheral neuropathy associated with IgM monoclonal gammopathy of unknown significance is a common disorder, while the association of paraproteinaemic neuropathies with haematological malignancies is far less frequent. We report a 76-year-old patient with a subacute and rapidly progressive sensorimotor demyelinating polyneuropathy causing sensory ataxia, painful paraesthesias and marked motor and sensory deficit in four limbs. Monoclonal gammopathy of IgM type associated with a rectal low-grade B-cell non-Hodgkin lymphoma was detected. Research for anti-MAG and antiganglioside autoantibodies including anti-GM1 and anti-GQ1b evidenced a high titre of IgM antibodies against the disialosyl group of GD1b. This is the first report on a paraproteinaemic polyneuropathy with IgM autoantibodies against glycolipid GD1b associated with B-cell lymphoma. The IgM type of these autoantibodies suggests that they represent all or part of the paraprotein produced by lymphoma cells.

Neurophysiology of spasms.

Spasms are a form of epileptic seizure typical of infancy. From a clinical point of view, the child presents a flexor-extensor movement involving the trunk and limbs and lasting about 1s. Although asymmetry can be present, the seizure involves both sides of the body. The ictal discharge most frequently associated with spasms in West syndrome (WS) is a diffuse triphasic slow high-amplitude wave and less frequently a low-amplitude brief rapid rhythm. The origin of the spasm in WS and classification as either partial or generalized seizure are the subject of much discussion. Factors supporting partial origin include: interictal electroencephalography (EEG) characterized by multifocal anomalies; high incidence of focal cortical lesions and remission of spasms following surgical removal of focal lesions. Factors supporting generalized origin are: clinical involvement of the entire body; mostly generalized ictal EEG pattern; existence of idiopathic cases and possibility of spasms immediately following a partial seizure like a particular form of secondary generalization. In our opinion, the categories of 'partial' and 'generalized' seizures are not applicable to spasms in WS. Sometimes the spasms in WS can be observed together with other types of partial or generalized seizures. Polygraphic recordings have demonstrated that despite being clinically similar, each spasm is different from the other because of a variable sequence in muscular contraction. These data support the peculiar nature of the spasm in WS that could be a subcortical phenomenon that requires a cortical trigger.

Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome).

Early-infantile epileptic encephalopathy (EIEE) with suppression-bursts is a severe neonatal epileptic encephalopathy. The etiology is multiple, with cerebral malformations as the more frequent. We review the clinical and video/EEG aspects of eight infants with EIEE. These infants, aged between 4 and 70 days at the time of video/EEG recordings, were studied in relation to their clinical and video/EEG characteristics, evolution, persistence of suppression-burst pattern and etiology. Seven of the eight infants showed an ictal clinical sign correlated to the burst of the suppression-burst pattern, four of whom died within 11 months of age. The other three are alive. One, now aged 4 years, underwent surgery for hemimegalencephaly and is seizure-free, with good neurological outcome. One, now aged 9 months, was pyridoxine-dependent and she is seizure-free, and with normal neurological evolution under pyridoxine therapy. One, now aged 3 years and 9 months, is seizure-free, but with severe neurological and cognitive impairment. The only child who did not show a clinical ictal correlation of burst is also alive, now aged 3 years and 9 months, with drug-resistant epilepsy, and severe neurological and cognitive deficits. With regard to the etiology, three showed structural abnormalities, two more showed some signs of prenatal origin of neurological disease, and three had metabolic etiology. Our study confirms that EIEE is a severe age-dependent early epileptic encephalopathy. The etiology is mostly malformative. The prognosis is poor regarding motor and cognitive development, seizures, as well as life expectancies. The presence of an ictal burst of the suppression-burst pattern usually correlates with a negative outcome.

Benign myoclonus of early infancy.

Benign myoclonus of early infancy, first described by Fejerman and Lombroso, is a paroxysmal phenomenon of the first 2 years of life which occurs in neurologically healthy infants during wakefulness, and is usually triggered by excitement or frustration. We studied the neurophysiological features of the phenomenon in five children, aged 7 to 11 months, who were monitored by video-EEG recording, and by polygraphic recording in 3 of the 5 cases. The phenomenon is characterized by a shudder-type, paroxysmal motor manifestation involving mainly the trunk and sometimes the head, associated with tonic limb contractions of variable intensity, from hardly noticeable to more sustained. The EEG counterpart never showed modifications, the polygraphic study demonstrated a brief tonic limb contraction. The clinical manifestation should not be confused with the spasms of epileptic infantile spasms syndrome, or with tonic reflex seizures of early infancy. Although the phenomenon is already widely known, its polygraphic recording is rarely reported in literature. The polygraphic data of our patients contributes to the diagnosis and understanding of the pathophysiology of this paroxysmal manifestation.

Repetitive sleep starts in neurologically impaired children: an unusual non-epileptic manifestation in otherwise epileptic subjects.

Sleep starts, also called hypnagogic or hypnic jerks, are bilateral, sometimes asymmetric, usually single, brief body jerks that coincide with sleep onset. We describe sleep starts occurring repetitively in three epileptic children with spastic-dystonic diplegia and mental retardation. Repetitive sleep starts began at age 18 months in two children and at 9 months in the third. All three children had had feto-neonatal asphyxia; two presented with spastic and one with dystonic tetraparesis. One had West syndrome and two had partial motor seizures in the first year of life. Seizures were controlled in all three patients by antiepileptic drug therapy. Video/EEG recordings of all the children during the afternoon nap revealed clusters of sleep starts during the transition between wakefulness and sleep. Cluster lasted 4-15 min and comprised from twenty to twenty-nine contractions. The EEG counterpart of the event sometimes showed an arousal response, at times inducing complete awakening. Repetitive sleep starts should be recognized and clearly differentiated from epileptic seizures, especially if they appear in epileptic subjects. In neurologically compromised patients, they could represent an intensification of an otherwise normal event, due to the lack of strong inhibitory influence of the pyramidal tract resulting from the pyramidal lesion.