Emma Frasson

Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy

Corticobasal degeneration is a sporadic form of tauopathy, involving the cerebral cortex and extrapyramidal motor system. A series of affected subjects was genotyped for a set of genetic markers along the tau protein gene. A specific haplotype is significantly overrepresented in patients versus controls. This haplotype is the same already reported in association with progressive supranuclear palsy. These data show that corticobasal degeneration and progressive supranuclear palsy, in addition to several clinical, pathological, and molecular features, may have the same genetic background. Ann Neurol 2000;47:374–377

Somatosensory disinhibition in dystonia

Despite the fact that somatosensory processing is inherently dependent on inhibitory functions, only excitatory aspects of the somatosensory feedback have so far been assessed in dystonic patients. We studied the recovery functions of spinal N13, brainstem P14, parietal N20, P27, and frontal N30 somatosensory evoked potentials (SEPs) after paired median nerve stimulation in 10 patients with dystonia and in 10 normal subjects. The recovery functions were assessed (conditioning stimulus: S1; test stimulus: S2) at interstimuls intervals (ISIs) of 5, 20, and 40 ms. SEPs evoked by S2 were calculated by subtracting the SEPs of the S1 only response from the SEPs of the response to the paired stimuli (S1 + S2), and their amplitudes were compared with those of the control response (S1) at each ISI considered. This ratio, (S2/S1)*100, investigates changes in the excitability of the somatosensory system. No significant difference was found in SEP amplitudes for single stimulus (S1) between dystonic patients and normal subjects. The (S2/S1)*100 ratio at the ISI of 5 ms did not significantly differ between dystonic patients and normal subjects, but at ISIs of 20 and 40 ms, this ratio was significantly higher in patients than in normals for spinal N13 and cortical N20, P27, N30 SEPs.

Temporal discrimination of somesthetic stimuli is impaired in dystonic patients.

Clinical and experimental evidence documents abnormal somatosensory functions in dystonia. Despite the fact that somatosensory processing is inherently temporal, mainly spatial aspects of somatosensory functions have so far been assessed in dystonic patients. Seven patients with idiopathic dystonia and nine healthy controls were given pairs of non-noxious electrical stimuli separated by different time intervals and asked to report if they perceived single or double stimuli. Somesthetic temporal discrimination thresholds (STDT) were obtained by computing the shortest time interval at which stimuli, applied to the left or the right hand, were perceived as separate. STDT were significantly higher in dystonic than in controls thus showing for the first time that temporal and not only spatial somatosensory processing is altered in dystonia.

Deficits of temporal discrimination in dystonia are independent from the spatial distance between the loci of tactile stimulation.

To assess whether spatial variables influence deficits of temporal somesthetic discrimination in dystonic patients, 10 patients with idiopathic dystonia and 12 healthy controls were tested with pairs of non‐noxious electrical stimuli separated by different time intervals. Stimuli were delivered: (1) to the pad of the index finger (same‐point condition), (2) to the pad and to the base of the index finger (same‐finger condition), and (3) to the pad of the index and ring fingers (different‐finger condition). Subjects were asked to report whether they perceived single or double stimuli in the first condition and synchronous or asynchronous stimuli in the second and third conditions. Somesthetic temporal discrimination thresholds (STDTs) were obtained by computing the shortest time interval at which stimuli, applied to the left or the right hand, were perceived as separate in the first condition or asynchronous in the second and third conditions. STDTs were significantly higher in dystonic patients than controls in all three conditions. In both dystonia patients and controls, STDTs resulted highest in conditions whereby stimuli were maximally separated in space. Results extend current knowledge of deficits of somesthetic temporal discrimination in dystonia by showing that temporal deficits are not influenced by spatial variables.

Botulinum Neurotoxin Type A Injections for Vaginismus Secondary to Vulvar Vestibulitis Syndrome

OBJECTIVE: To investigate whether botulinum neurotoxin type A improves vaginismus and study its efficacy with repeated treatments. METHODS: Outpatients were referred because standard cognitive–behavioral and medical treatment for vaginismus and vulvar vestibular syndrome failed. From this group, we prospectively recruited consecutive women (n=39) whose diagnostic electromyogram (EMG) recordings from the levator ani muscle showed hyperactivity at rest and reduced inhibition during straining. These women were followed for a mean (±standard deviation) of 105 (±50) weeks. Recruited patients underwent repeated cycles of botulinum neurotoxin type A injected into the levator ani under EMG guidance and EMG monitoring thereafter. At enrollment and 4 weeks after each cycle, women were asked about sexual intercourse; underwent EMG evaluation and examinations to grade vaginal resistance according to Lamont; and completed a visual analog scale (VAS) for pain, the Female Sexual Function Index Scale, a quality-of-life questionnaire (Short-Form 12 Health Survey), and bowel and bladder symptom assessment. RESULTS: At 4 weeks after the first botulinum neurotoxin type A cycle, the primary outcome measures (the possibility of having sexual intercourse, and levator ani EMG hyperactivity) both improved, as did the secondary outcomes, Lamont scores, VAS, Female Sexual Function Index Scales, Short-Form 12 Health Survey, and bowel–bladder symptoms. These benefits persisted through later cycles. When follow-up ended, 63.2% of the patients completely recovered from vaginismus and vulvar vestibular syndrome, 15.4% still needed reinjections (censored), and 15.4% had dropped out. CONCLUSION: Botulinum neurotoxin type A is an effective treatment option for vaginismus secondary to vulvar vestibular syndrome refractory to standard cognitive–behavioral and medical management. After patients received botulinum neurotoxin type A, their sexual activity improved and reinjections provided sustained benefits. LEVEL OF EVIDENCE: III

Evidence for an abnormal cortical sensory processing in dystonia: selective enhancement of lower limb P37-N50 somatosensory evoked potential

We evaluated brain stem P30, contralateral frontal N37, and the vertex‐ipsilateral central P37, N50 somatosensory evoked potentials (SEPs) obtained in response to stimulation of the tibial nerve in 10 patients with idiopathic dystonia. Results were compared with those obtained in 10 healthy subjects matched for age and sex. The amplitude of the brain stem P30 potential and of the contralateral frontal N37 response in dystonic patients was not significantly different from that recorded in normal subjects. The vertex‐ipsilateral central P37‐N50 complex, which is thought to originate in the pre‐rolandic cortex, was significantly enhanced in patients compared with the control group. These results suggest the enhancement of the vertex‐ipsilateral central P37‐N50 complex might reflect an abnormal response to somatosensory inputs of a precentral cortex which is excessively activated because of a disorder of the basal ganglia. Such inefficient sensory processing in motor areas might contribute to motor impairment in dystonia.

Nerve stimulation boosts botulinum toxin action in spasticity

Spasticity leads to functional and structural changes in nerves and muscles, which alter skeletal muscle function. To evaluate whether short‐term electrical nerve stimulation (NS) improves the effect of botulinum toxin in spastic skeletal muscle, we studied changes in the amplitude of the compound muscle action potential (CMAP) recorded from the extensor digitorum brevis (EDB) muscle in response to peroneal nerve stimulation at the ankle after injection of botulinum toxin type A (BTXA) alone or combined with short‐term NS. In paraparetic patients, both EDB muscles were injected with BTXA; and NS was applied to one EDB muscle alone. All patients received a 30‐minute session of electrical NS once a day for 5 consecutive days after BTXA injection. We used two different stimulation frequencies (low‐frequency, 4 Hz; and high‐frequency, 25 Hz). EDB‐CMAP amplitudes were evaluated before BTXA injection (day 0) and changes in CMAP amplitude, expressed as a percentage (CMAP%), were measured at various time points over a 30‐day period after BTXA injection. We compared changes in the CMAP% amplitude on the stimulated and contralateral nonstimulated sides. We also studied the electromyographic activity recorded from EDB muscles over a 30‐day period. CMAP% amplitudes measured at all time points after BTXA injections were significantly reduced in both EDB muscles. On days 4, 10, and 15, the CMAP% amplitude reduction was significantly greater for the low‐frequency stimulated EDB than for the contralateral nonstimulated EDB. No significant differences in CMAP% were observed for the high‐frequency stimulated and nonstimulated EDB. After BTXA injection, spontaneous activity appeared in both EDB muscles; but it appeared earlier and involved larger areas in the stimulated than in the nonstimulated EDB. In conclusion, short‐term NS accelerates the effectiveness of intramuscular BTXA injections on the neuromuscular blockade in patients with spastic paraparesis and could induce a rapid and persistent improvement in spasticity. Its action probably arises mainly from low‐frequency NS.

Central nervous system abnormalities in vaginismus.

OBJECTIVE To investigate possible altered CNS excitability in vaginismus. METHODS In 10 patients with primary idiopathic lifelong vaginismus, 10 with vulvar vestibulitis syndrome accompanied by vaginismus and healthy controls we recorded EMG activity from the levator ani (LA) and external anal sphincter (EAS) muscles and tested bulbocavernosus reflex (BCR). Pudendal-nerve somatosensory evoked potentials (SEPs) were tested after a single stimulus. Pudendal-nerve SEP recovery functions were assessed using a paired conditioning-test paradigm at interstimulus intervals (ISIs) of 5, 20 and 40ms. RESULTS EMG in patients showed muscular hyperactivity at rest and reduced inhibition during straining. The BCR polysynaptic R2 had larger amplitude (p<0.01) and longer duration (p<0.01) in patients from both groups than in controls. In controls, paired-pulse SEPs were suppressed at the 5ms ISI for N35-P40 (p<0.05) and P40-N50 ms (p<0.001) and facilitated at the 20ms ISI for N35-P40 (p<0.05) and P40-N50 (p<0.05). No significant differences were found in the paired-pulse N35-P40 in patients and controls but the cortical P40-N50 at 20 ISI was facilitated in patients (p<0.05). CONCLUSIONS EMG activity is enhanced and the cortical SEP recovery cycle and BCR are hyperexcitable in vaginismus. SIGNIFICANCE The neurophysiological abnormalities in patients with vaginismus indicate concomitant CNS changes in this disorder.

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

OBJECTIVE To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinsons disease (PD). METHODS Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. RESULTS In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. CONCLUSIONS Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

Botulinum Toxin Type A vs Type B for Axillary Hyperhidrosis in a Case Series of Patients Observed for 6 Months

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