Chiara Scarpini

Clonus in man: a rhythmic oscillation maintained by a reflex mechanism

The mechanisms underlying clonus were studied in 7 patients with spasticity of the lower limbs arising from upper motor neuron lesions. Clonus sensitivity to resetting was studied by evoking a soleus H reflex at different time intervals between two successive clonic beats. The relationship between the interval separating the H reflex from the preceding beat and the inter-beat interval in which the H reflex was delivered was used to calculate the resetting index. A high resetting index, close to 1.0, was found. Calf compression, applied to the upper third of the leg to block group I afferent fibres from gastrocnemius-soleus muscle, completely abolished ankle clonus within 10 min of the onset of compression. Clonus disappearance was preceded by a progressive reduction in duration and frequency. Finally, evidence is presented that clonus duration is contingent upon joint angle and therefore presumably on the amount of stretch placed on the triceps surae muscle group. Our findings demonstrate that clonus is largely dependent on reflex and mechanical factors and do not confirm the recent hypothesis that clonus relies on a central spinal generator.

Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study

We report the electrophysiological follow-up of five cerebrotendinous xanthomatosis patients treated for 11 years with chenodeoxycholic acid (CDCA). Nerve conduction velocity (NCV) was reduced in three cases. P100 latency of visual evoked potentials was delayed in four cases, interpeaks I-III and I-V of brainstem auditory evoked potentials (BAEPs) was increased in two and interpeak N13-20 of upper limb somatosensory evoked potentials (SEPs) was slowed in one. After 4 months of therapy with CDCA, NCV was normal and did not show any significant change during the 11 years of observation. Central motor conduction time of motor evoked potentials (MEPs) and N24-P40 interpeak latency of lower limb SEPs were increased in five and four cases, respectively, in spite of 2/3-year treatment with CDCA. Improvement of evoked potentials, especially of MEPs and SEPs, was slower and continued over the whole 11-year period. The size of xanthomas slightly decreased in some patients during treatment and the clinical manifestations stabilized, avoiding progressive worsening, but there was no significant improvement in neurological deficit. Two sisters of patients who never took CDCA showed progressive worsening of clinical manifestations, upper limb SEPs and BAEPs.

BAEP changes in Leber's hereditary optic atrophy: further confirmation of multisystem involvement

A neurophysiological study of 11 patients belonging to 5 families affected by Lebers hereditary optic atrophy is reported. Electromyography, nerve conduction velocities and somatosensory evoked potentials were normal. Visual evoked potentials were absent or delayed, desynchronized and reduced in amplitude. Brainstem auditory evoked potentials were anomalous in 64% of subjects all without hearing defects. These changes which have never before been reported, confirm multisystem involvement in this disease.

Palatal myoclonus and unusual MRI findings in a patient with membranous lipodystrophy

We describe an Italian male patient, deceased at 29 years of age, affected with a syndrome characterized by childhood-onset seizures, mental disorders, motor dysfunction and bilateral palatal myoclonus. Skeletal X-ray examination showed diffuse osteopenia of the tubular bones, and cyst-like lesions in the carpal, metacarpal and tarsal bones bilaterally and in the proximal end of the right femur. Skin biopsy showed subcutaneous and adipose tissue containing membranocystic structures. Cerebral MR and CT scans showed fronto-temporal atrophy, altered signal of the white matter and mineralization of the caudate and dentate nuclei. These findings strongly recall polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, but in the present case, bone alterations were not prominent; moreover, palatal myoclonus has never previously been described in this syndrome.

Evidence for Renshaw cell-motoneuron decoupling during tonic vestibular stimulation in man.

The influence of static head-body tilts in the sagittal plane on the activity of Renshaw cells coupled to the soleus extensor alpha-motoneurons was studied in eight human subjects. Head-body rotation was carried out using a tilting seat and its effect was evaluated at 80 degrees (normal sitting position) and at 40 degrees of backward inclination (nose-up). Renshaw cell activity was assessed through a specially designed method of paired H-reflexes first described by Bussel and Pierrot-Deseilligny. alpha-Motoneuron excitability was also independently studied by mapping a reference H-reflex amplitude as a function of static head-body displacements. In almost all subjects Renshaw cell activity was increased at 40 degrees backward inclination with respect to control values at 80 degrees. These changes were attributed to the tonic labyrinthine reflexes capable of decoupling Renshaw cell activity from their motoneurons when the body was tilted backward from the upright position. We discuss the hypothetical functional modalities of the recurrent inhibitory circuit during postural adjustments elicited by labyrinthine input.

ATAXIA‐TELANGIECTASIA: SOMATOSENSORY,‘BRAINSTEM AUDITORY. AND MOTOR EVOKED POTENTIALS IN SIX PATIENTS

Six patients with ataxia‐telangiectasia were given neurophysiological examinations. The patients had progressive sensorimotor axonal neuropathy that had begun at about age eight years. Brainstem auditory evoked potentials (BAEPs) showed central alterations in two of four cases. Somatosensory (BAEPs) and motor evoked potentials (MEPs) were altered in four of five cases. In the advanced stage of the disease the neurophysiological findings, except BAEPs and MEPs, resembled those in Friedreichs ataxia. MEP and BAEP results may therefore be useful for differential diagnosis.

The Primrose syndrome with progressive neurological involvement and cerebral calcification

Sirs: The Primrose syndrome is a rare disorder, first described in 1982 in a man with mental retardation, progressive muscle wasting, ossified ear cartilage, cystic changes in the humeral and femoral heads, paracentral posterior cataract and hearing loss [4]. Two other cases were later described [1, 3]. We report a new case, the first described in a woman, with the classical features of the Primrose syndrome, associated with late-onset progressive gait ataxia, pyramidal signs and cerebral calcification. The patient, a 49-year-old woman with delayed motor developmental milestones and severe mental retardation, was born from non-consanguineous parents. The mother is reported to have had a clumsy gait since adolescence. At 40 years of age, diabetes was diagnosed in the patient. Six years later, she underwent cataract surgery on the right eye. At that time, gait problems appeared. At 49 years of age, she was admitted to our department because of progressive worsening of gait disturbances, with inability to walk unaided. General examination showed mild dysmorphic features (Fig. 1) with smooth skin of the legs and numerous dyschromic spots, sparse and thin hair, bilateral enophthalmos, pseudophakia of the right eye, ptosis and cataract in the left eye, depressed nasal bridge, prognathism, completely rigid helices and bilateral pes cavus. Neurological examination revealed severe mental retardation, frequent confabulation, mild deafness, severely impaired spastic-ataxic gait, positive Romberg sign, slight hypertonia, mild muscular atrophy of the limbs, upper limb areflexia, brisk tendon reflexes in the legs, bilateral ankle clonus and Babinski sign. Laboratory investigations revealed normal values for routine chemistry and the following blood test results: thyroxine, thyroidstimulating hormone, folate, vitamin B12, ceruloplasmin, amino acids, lactic and pyruvic acid, cholestanol, lysosomal enzymes activity (α-fucosidase, α-mannosidase, α-galactosidase, hexosaminidase A and B; arylsulfatase A and B; β-glucuronidase; galactocerebrosidase), seroly for syphilis, urinary phosphate and calcium levels were all normal. EEG, ECG and the chromosome map were normal. Dermatological examination showed hypopigmented atrophic lesions with slight sclerosis of the limbs. Total body radiography of the skeleton showed generalized, severe osteopenia (Fig. 2 a, b). Electroneurography showed mild, mainly sensory axonal neuropathy. Brain CT showed areas of dense calcification in both heads of the caudate nuclei while areas of less dense calcification were seen in both globi pallidi and in the anterior limb of the left internal capsule; dense calcification of both external ears was also evident (Fig. 3 a, b). Brain MRI failed to show further abnormalities. A muscle biopsy specimen was suggestive of neurogenic atrophy. The clinical and radiological hallmarks of the patient reported here strongly suggest a diagnosis of Primrose syndrome [4]. The only three previously reported cases were men with a negative family history. Beside the classical signs of Primrose syndrome, they all showed common craniofacial dysmorphism and a slowly progressive neurological course with gait disturbances particularly severe in Primrose’s original patient [4]. However, the neurological involvement was neither well documented nor considered a characterizing feature. The female patient described here adds to the other few cases and suggests that: i) Primrose syndrome is not confined to males; ii) facial dysmorphism and late-onset, progressive neurological manifestations are part of the clinical phenotype; iii) neurological involvement is also proved by the presence of cerebral calcification, reported for the first time in our patient. In this regard, we recommend that CT be performed to search for cerebral LETTER TO THE EDITORS

Leber's optic atrophy: VEP and BAEP changes in 16 asymptomatic subjects

We demonstrated anomalies in brain stem evoked potentials (BAEPs) in 64% of a group of patients with Leber’s optic atrophy (1). Colour discrimination, fundus oculi and fluorangiographic alterations have been reported by some authors in several asymptomatic subjects (2-4), but visual evoked potential (VEP) findings are contradictory. Livingstone et al. reported only one subject (a male at risk) with abnormal VEPs of 16 asymptomatic members of a family (2), while Carrol & Mastaglia found anomalies (delayed or bifid P2 or increased temporal dispersion) in 12 of 16 asymptomatic subjects of another family (4). We studied 13 women belonging to 5 affected families: 6 mothers of affected subjects (definite carriers) and 7 sisters of affected subjects without sons or with healthy sons (potential carriers) (mean age was 44.5 years; range 14-63 years). We also studied 3 men at risk (13, 16 and 18 years old), brothers of affected subjects. All subjects underwent routine neurophthalmological examination and investigation of VEPs and BAEPs; the details of methods have already been published (1). None had visual or hearing symptoms, only 2 had simple refraction defects corrected by lenses; 9 subjects (6 women of whom 2 were definite and 4 potential carriers and all 3 men) had VEP alterations consisting in N 1-N2 interpeak latency (IPL) increase, associated with P2 delay; only 2 cases had N 1-P2 amplitude reduction. The percent increase of VEP changes was within 1 6 4 5 % of mean control values; 5 subjects (3 women and 2 men) demonstrated moderate BAEP abnormalities: 4 showed bilateral 1-11 and 1-111 IPL increase associated in 3 with monolateral I-V IPL delay. One man had bilateral I-V IPLs delay associated with monolateral 1-11 and 1-111 IPL increase. 111-V IPLs were normal in all. The BAEP changes were relatively moderate and the percent increase of the IPLs was within 11-53 % of the man control values. Four subjects had BAEP and VEP alterations, a definite carrier demonstrated only BAEP changes, and the other 5 had only VEP abnormalities. One-way analysis of variance (ANOVA) was performed for BAEP and VEP data between our 13 asymptomatic women (26 sides of stimulation) and the control group and between definite and potential carriers. This analysis revealed significant differences (p < 0.001) between 13 carriers and control group for P2 latency (F = 32.22) and Nl-N2 (F = 19.17), 1-11

Early-onset benign limb-girdle myopathy with contractures and facial involvement affecting a father and daughter

We describe a father and daughter with early-onset benign limb-girdle myopathy and contractures of elbows and hands, resembling Bethlem disease. Muscle biopsy showed a pattern of dystrophy with non specific mitochondrial changes. In both patients there was unusual facial muscle weakness. We discuss the nosologic position of Bethlem myopathy and suggest that facial involvement may be an additional feature of this disease.

Autosomal recessive paraparesis with amyotrophy of hands and feet and white matter lesions

We report two siblings with a hitherto undescribed syndrome of autosomal recessive spastic paraparesis accompanied by amyotrophy of hands and feet, and mental deterioration. Laboratory tests showed signs of lower motoneuron involvement in the four limbs, more accentuated in the distal regions. Brain MR showed bilateral symmetrical white matter lesions. We discuss the nosological status of this syndrome in relation to other similar forms of “complicated” spastic paraparesis.