Giovanni Antonio Cocco

Levetiracetam in stiff-person syndrome

We studied the effects of oral levetiracetam (LEV) (500 mg twice daily) in three women with stiff-person syndrome in a single-blind, placebo-controlled study. The severity of muscle rigidity and of paroxysmal symptoms was assessed by EMG and clinically by a rating scale of 0–4 and by the Patients Global Impressions Scale. LEV was well tolerated. On active treatment all patients improved as assessed by any of the objective or subjective outcome measures. No response was noticed on placebo. Our data indicate that in patients with SPS, LEV is well tolerated and has a therapeutic role in the management of both muscle stiffness and life-threatening paroxysmal respiratory spasms.

Disfluent speech in patients with partial epilepsy: beneficial effect of levetiracetam.

PURPOSE The aim of this study was to evaluate the clinical effects of levetiracetam (LEV) in patients with partial epilepsy and disfluent speech. METHODS Five consecutive patients with partial epilepsy and disfluent speech resulting from developmental or neurogenic stuttering were enrolled in a 9-week, open-label, prospective study. LEV was given in combination with carbamazepine (CBZ) or phenytoin (PHT) at dosages ranging from 500 to 1500mg twice daily. The severity of stuttering was assessed with the verbal fluency test (VFT), and with the patient global impression of improvement (PGI), at baseline and after 9weeks. Electroencephalography and serum monitoring of CBZ and PHT levels were done before and after the study. Seizure frequency was monitored. RESULTS After LEV therapy, verbal fluency for all patients, as measured by the VFT, improved from 25% at baseline to 64%, as did the speed of oral reading, from 5 to 23%. On the PGI, all patients rated themselves as better and as having less disfluent speech after LEV therapy. For four patients with incomplete control of their seizures, the seizure count decreased by more than 50% after LEV therapy. The beneficial effect of LEV on verbal disfluency demonstrated on the PGI persisted for the entire period of observation, which ranged from 7 to 11 months. CONCLUSIONS As an add-on therapy, LEV seems to improve verbal fluency in patients with partial epilepsy and disfluent speech. This effect seems unrelated to the antiepileptic activity of the drug. A placebo-controlled trial of LEV in patients with this kind of verbal disfluency is warranted.

Focal and secondarily generalised convulsive status epilepticus induced by thiocolchicoside in the rat

The objective of this study was to document the convulsant properties of thiocolchicoside in rats, and to characterise the electroclinical pattern of epileptic seizures. Experiments were carried out in three groups of male Wistar rats: in group A, thiocolchicoside was applied topically to the pia, or given by microinjection to the cerebral cortex (2 microg/microl); in group B, the drug was administered parenterally (6 mg/kg) to rats with minimal lesions of the dura and arachnoid membranes; in group C, thiocolchicoside was administered parenterally (up to 12 mg/kg) to intact rats. In all animals, electroclinical activity was continuously monitored for at least 3 hours after thiocolchicoside injection or application. In group A, electrographic and behavioural activity of focal motor seizures occurred in 100% of animals, developing into a focal status epilepticus; in group B, a multifocal epileptic pattern with secondary generalisation, clinically characterised by clonic or tonic-clonic seizures occurred in 100% of animals, until a secondarily generalised convulsive status epilepticus; in group C, none of animals showed either electrographic or behavioural seizure activity. Our study documents that thiocolchicoside has a powerful convulsant activity in the rat, perhaps due to an antagonistic interaction of the compound with a cortical subtype of the GABA(A) receptor.

Valproate-induced parkinsonism, glial cells and Alexander's disease

A 39-year-old, right-handed woman was admitted in October 2005, because of progressive bladder dysfunction since age 35, the appearance of a restless legs syndrome at age 38 treated with pramipexole and a progressive blurred speech in the last five months. Family history was negative for neurological pathologies. Neurological examination showed no cognitive impairment, a severely dysarthric speech, hyperactive tendon reflexes, a mild gait ataxia and a rhythmic palatal myoclonus at 1.5-2 Hz. Physical examination, electrocardiogram, electroencephalogram, peripheral blood and cerebrospinal fluid parameters were all normal. T2 weighted and FLAIR brain Magnetic Resonance Imaging (MRI) revealed bilateral, highsignal-intensity areas posteriorly in the periventricular white matter, descending pyramidal tracts of the medulla and deep cerebellar white matter (Fig. 1). Patients DNA direct sequencing revealed two point mutations in the heterozygous form in the glial fibrillary acidic protein gene (GFAP), respectively in exon 1 and exon 2. In exon 1, a G to A substitution at nucleotide 209 was shown, resulting in change of arginine to glutamine at position 70 (R70Q), in exon 2, instead, a G to A substitution at nucleotide 469, resulting in change of aspartic acid to asparagine at position 157 (D157N) (Caroli et al., 2007; Li et al., 2006). Valproate administration at increasing doses, until 500mg twice daily, for the palatal myoclonus, led within 3 months to bradykinesia and rigidity. Neurological examination according to the Unified Parkinsons Disease Rating Scale (UPDRS) revealed the following motor scores: facial expression 2; speech 1; body bradykinesia 3; rigidity neck 2, right arm 2, left arm 2, right leg 2, left leg 2; finger taps right 1, left 2; leg agility right 2, left 2; arise from chair 1; posture 1; gait 1; postural stability 1 (total UPDRS motor score=27), corresponding to stage 2.5 of the Hoehn/Yahr Parkinsons Disease Scale. There was no cognitive impairment (Mini Mental State Examination score of 30). Blood valproate levels (EMIT system) ranged between 43-51 μg/mL (range values: 40-100 μg/mL). Valproate was ineffective on palatal myoclonus. Repeated laboratory findings were within normal limits. After valproate discontinuation, the parkinsonism cleared within one month (UPDRS motor score=0). No relapses of parkinsonian symptoms were observed in the 16 months following the valproate withdrawal. 3. Discussion

“Acquired” hepatocerebral degeneration in a patient heterozygote carrier for a novel mutation in ATP7B gene

Acquired hepatocerebral degeneration (AHD) is a rare type of hepatic encephalopathy characterized by neuropsychiatric symptomatology, and peculiar neuroradiologic findings, without the clinical evidence of Wilson’s disease (WD). We studied a patient with AHD responsive to penicillamine who was heterozygote carrier for a novel mutation in the ATP7B gene, and discussed the possible role of the mutation in facilitating the appearance of the syndrome. A 37-year-old man with liver cirrhosis related to chronic hepatitis C was admitted because of progressive consciousness impairment. Family history was negative for WD. Ammoniemia was 176 lmol/L (NR, 9–33 lmol/L); total bilirubin 1.71 mg/dL (NR, 0.2–1.3 mg/dL); serum albumin 2.6 g/dL (NR, 3.3–5 g/dL); AST 62 U/L (NR, 10–45 U/L). Electroencephalogram disclosed diffuse slow wave activity. After rifaximin, lactulose, and branched chain amino acid infusion, his arousal state went back normal in about 12 hours, and ammonia levels decreased to 94 lmol/L.