Domenico Mancia

Impairment of corneal pain perception in cluster headache

&NA; Despite many studies, the mechanisms underlying the pathogenesis of pain in cluster headache (CH) still remain obscure. An involvement of substance P (SP) containing neurons of the Gasserian ganglion and/or of the spinal trigeminal nucleus has recently been suggested, e.g., by impairment of inhibitory descending pathways on trigeminal nociceptive neurons. The electrically elicited corneal reflex was studied in 21 CH patients (15 in active phase, 6 in remission). This method allows simultaneous measurements of the trigemino‐facial reflex and corneal pain perception. A significant reduction of pain thresholds (more evident on the pain side) was observed in CH during the active phase, while normal values were recorded during the remission phase. Ten out of 15 patients in the active phase showed a significantly reduced corneal pain threshold on the pain side, while tactile sensibility was normal. Moreover, latency, amplitude and duration of the corneal reflex were normal for both painful and painless stimulations during both phases. The threshold of the nociceptive muscular response in the active phase was significantly reduced, suggesting that the excitability of trigeminal nociceptive neurons or of the motor neurons is increased in CH. The results agree with the hypothesis that a reversible impairment of several integrative functions, including the activity of trigeminal pain control system, exists in CH during the active phase.

Frontal intermittent rhythmic delta activity (FIRDA) in patients with dementia with Lewy bodies: a diagnostic tool?

Abstract. The accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) remains poor, especially in early phases of the disease, in spite of applying current consensus diagnostic criteria. The need for supportive diagnostic tools is therefore warranted. In this study EEG recordings showed a main pattern of bilateral frontal intermittent rhythmic delta activity (FIRDA) in 7 of 10 patients, aged 58–83 years, 8 of whom were diagnosed as affected by “probable” and 2 by “possible” DLB. Conversely, the same EEG abnormality was found only in 2 of 9 age-matched patients, 8 of whom had “probable” and 1 “possible” Alzheimers disease, according to NINCDS-ADRDA criteria, taken as controls. The degree of cognitive impairment was comparable among the two groups of patients. If these findings will be confirmed in a larger series, FIRDA, even though an aspecific EEG pattern, could be of value in improving the diagnostic accuracy of DLB.

Acute sensory and autonomic neuropathy: possible association with coxsackie B virus infection.

This report describes a 26 year old woman with a Coxsackie B virus infection complicated by an acute pandysautonomic and sensory neuropathy. Electrophysiological studies suggested an axonal neuropathy. A sural nerve biopsy performed early in the disease showed axonal degeneration with a virtual absence of unmyelinated fibres and moderate loss of myelinated fibres, mainly affecting the small fibres; this differs from previous reports. An immune-mediated or direct virus action might explain the pathogenesis of this unusual evolution of a viral infection.

Reversible valproate-induced extrapyramidal disorders.

Summary: We observed transient parkinsonism in 2 young epileptic patients with valproate (VPA) therapy. Complete recovery from extrapyramidal disorder occurred spontaneously in a few weeks. The lack of apparent susceptibility related to age and to VPA dosage, the rapid recovery from the extrapyramidal reaction, and the prevalence of negative signs such as bradykinesia and bradyphrenia can be considered the main clinical findings of this disease process. Pathophysiologic mechanisms of this rare “toxic” reaction remain unknown, although a transient imbalance between functionally reciprocal subgroups of GABA pathways leading to remediable dopa‐mine inhibition might be hypothesized.

Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis

OBJECTIVE (1) to develop a method for masseteric repetitive nerve stimulation (RNS) and to obtain normative data for amplitude and area decrement of the muscle (M) response. (2) To investigate myasthenia gravis (MG) patients with masseteric RNS. Masticatory muscles are frequently affected in MG, but no RNS test is available to investigate this district. METHODS Fifteen healthy subjects and 17 MG patients were examined. The masseteric nerve was stimulated by a monopolar needle (cathode), inserted between the mandibular incisure and the zygomatic arch, and a surface electrode (anode), on the contralateral cheek. Masseteric M response was recorded using surface electrodes on the muscle belly and below the mandibular angle. Stimuli were delivered at 3 Hz in trains of 9, at rest and after isometric effort. RESULTS Normal subjects: mean amplitude decrement was 0.3+/-1.2% at rest, and 1.9+/-1.3% after isometric effort. PATIENTS 15 patients (88%) were positive on masseteric RNS; in 3 of these it was the only positive RNS test. The extent of decrement observed in masseter muscle was significantly greater than in trapezius muscle. CONCLUSIONS Masseteric RNS is a simple and well-tolerated procedure; it offers a new possibility in testing the cranial muscles in disorders of neuromuscular transmission.

Motor-evoked potentials in masseter muscle by electrical and magnetic stimulation in intact alert man

The electromyographic responses of the masseter after different types of transcranial stimulation were recorded with surface and needle electrodes. Magnetic stimulation at 4 cm lateral to the vertex on the biauricular line elicited MEPs in the contralateral masseter (latency 6.9 ms) due to activation of motor cortex or adjacent elements along the cortico-nuclear pathway. The ipsilateral responses to the same stimuli and to more lateral ones had shorter latencies and were ascribed to direct stimulation of the trigeminal nerve, probably its intracisternal portion. This was also the probable origin of the ipsilateral MEPs after both anodic and cathodic bipolar electrical stimulation at 7 and 11 cm lateral to the vertex on the biauricular line.

Long-term efficacy of interferon-alpha in chronic inflammatory demyelinating polyneuropathy.

Sirs: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing immune-mediated disorder usually responsive to steroids, intravenous immunoglobulins (IVIg), plasma exchange (PE), or a combination of these treatments [2]. However, treatment failure in some patients requires the use of other immunosuppressive agents, such as cyclophosphamide or azathioprine. Some data are available for treatments with cyclosporin [1, 10], interferon-alpha 2 a (IFN-alpha) [4–6, 8], and interferon-beta 1 a (IFN-beta) [3, 7]. The use of IFNalpha has also been debated because of possible neurotoxic effects [9]. We report a patient with CIDP who became unresponsive to conventional treatments and experienced a dramatic and long-lasting improvement following a prolonged treatment with IFN-alpha. A 56-year-old woman came to our observation in June 1993 complaining of left hand paraesthesias and mild weakness for two months. Her past history was unremarkable. Routine haematological examinations gave normal findings. CSF proteins were elevated (115 mg/dL), with normal cell count. Serological tests for Lyme disease, HCV and HIV were negative. Serology for neurotropic viruses, EBV and CMV was negative. Immunoelectrophoresis showed no monoclonal components in both serum and urine. Antiganglioside antibodies were not detected in serum. In the following 3 months she progressively developed a severe symmetric weakness of proximal and distal limb muscles. At this time tendon reflexes were absent in the lower limbs and reduced in the upper limbs. Nerve conduction studies (NCS) showed an asymmetric sensory-motor polyneuropathy with mainly demyelinating features in all the commonly tested nerves in the four limbs. The diagnosis of CIDP was made and treatment with oral prednisone was started (75 mg/day), with no effect on the progression of disability. Steroids were therefore discontinued after 3 months. The patient was then treated with IVIg and PE, according to standard protocols, with partial benefit. In the following three years she became unresponsive to both treatments; azathioprine was discontinued after 21 days because of hepatotoxicity and cyclophosphamide, administered monthly at the dose of 1 g/m2 for 4 months, was ineffective. Three years after the onset of the disease, in June 1996, the patient was bedridden because of marked weakness and sensory ataxia; tactile anaesthesia involving the limbs, the lower trunk, and the alae nasi; she needed continuous assistance. Conduction blocks, defined as decrease of more than 50 % of M response area between distal and proximal sites, were present on median, ulnar and peroneal NCS. Distal M response amplitudes were significantly reduced and fibrillation potentials were evident on needle EMG of distal limb muscles, suggesting the coexistence of axonal damage. At this time treatment with IFN-alpha (Roferon®) was started at the dose of 3 million international units (MIU) s. c. two times a week, for 12 months. Clinical improvement was first noticed after 2 weeks, and 6 months later a complete functional recovery had been achieved. At this time she was able to run and sensory deficits had disappeared. Tendon reflexes were present in upper limbs and knees; ankle reflex was absent on the left and reduced on the right. Serial NCS showed progressive increase of distal M response amplitude and of conduction velocities; conduction blocks disappeared in all nerve segments (Fig. 1). LETTER TO THE EDITORS

Sural nerve abnormalities in sacral perineural (Tarlov) cysts

Sirs: Perineural cysts (PCs) are formed by ectasia of the perineural space of spinal nerve roots that occur at or distal to the dorsal root ganglion, most frequently at the lumbosacral level. We investigated electrophysiologically the sural nerves of 11 patients with sacral PCs, selected among the outpatients referred to our EMG laboratory in the last two years. We found sural sensory nerve action potential (SNAP) abnormalities in 5 (3 males and 2 females, aged 40–66 years). These five patients underwent a complete clinical evaluation and neurophysiological investigation. The main clinical and radiological data are summarized in Table 1. Common causes of acquired peripheral neuropathies were excluded by means of laboratory investigations. A clinical history was undertaken in order to rule out familial neuromuscular diseases or major spinal traumas. The presence of PCs was documented in all these cases by MRI scans of the lumbosacral spine. The cysts were bilateral in 3 cases. One patient (case 3) was asymptomatic; three patients (cases 1, 2 and 4) had been referred to our EMG laboratory for low back pain; one patient (case 5) complained of bilateral plantar pain and dysaesthesia. Sensory nerve conduction studies were performed on all the patients on the sural nerve, with surface recording electrodes in bipolar montage below the lateral malleolus and stimulating 14 cm proximally. The latency was measured at the negative peak and amplitude was measured peak to peak. SNAP amplitude was considered abnormal if it was lower than 7 μV, and sensory nerve conduction velocity (NCV) of the sural nerve was considered abnormal if it was lower than 36 m/s. Peroneal and tibial nerve motor conduction studies, including F waves, were performed according to standard methods [6]. Electroneurographic studies were also conducted on superficial peroneal, saphenous, median and ulnar nerves in the 3 patients in whom bilateral sural SNAP abnormalities were found (cases 1, 3 and 5). Nerve conduction studies were performed at skin temperature of 36°C, kept constant by means of an infrared lamp and a skin temperature sensor. The main electrophysiological findings are summarized in Table 1. Sural SNAP abnormalities were found on the same side as the cyst when the latter was unilateral, and bilaterally in patients with bilateral cysts. Motor nerve conduction studies were normal in all subjects. Saphenous and superficial peroneal SNAPs and upper limb nerve conduction studies were all normal in the 3 patients tested. Our findings show that PCs can in some cases be associated with reduced sural SNAP amplitude. The electroneurographic studies were directed to the sural nerve because it is composed of fibres originating mainly from the S1 and S2 roots [8], which are the most frequently affected by PCs. The concordance between the cyst side and the side of the reduced SNAP was extremely high: patients with unilateral cysts showed SNAP abnormalities only on the cyst side, and patients with bilateral cysts showed abnormalities on both sides. The sensory NCVs were slightly reduced in cases 1, 2 and 3, possibly owing to the loss of large-diameter sensory fibres. In patients 1, 3 and 5 the bilateral integrity of saphenous and superficial peroneal SNAPs showed that the amplitude reduction of sural nerve SNAPs was not due to length-dependent damage as in polyneuropathies [3]. Moreover, the clinical picture and laboratory investigations were not compatible with the diagnosis of polyneuropathy. Perineural cysts are symptomatic in 20 % – 25 % of cases, most frequently manifesting with low back pain and sciatica [4, 11]. Our patients complained mainly of senLETTER TO THE EDITORS

Petit Mai Status with Myoclonus: Case Report

The authors describe a case of petit mal status épisodes with myoclonus in a woman of 77 years, in whom the only preceding symptom was a grand mal attack at the âge of 70. In addition to a confusional state lasting several hours, the épisodes were characterized by the presence of massive myoclonic jerks. The jerks were closely related to multiple spikes of the generalized polyspikes and polyspike‐and‐wave complexes which characterized the EEG during the status. These épisodes often ended with a grand mal attack. Between status épisodes the patient was lucid and presented a negative neurological picture, although undoubted signs of intellectual deterioration were noted. The case is notable from the polygraphic point of view for the severity of the myoclonic involvement, and from the clinical point of view for the fact that the status was the sole epileptic symptomatology which appeared in old âge. This, together with other observations in the literature, suggests the existence of primarily generalized epilepsy occurring late in life, predominant probably in females, and assuming the features of confusional states or grand mal seizures.

Trigemino-facial inhibitory reflexes in idiopathic hemifacial spasm

We investigated trigemino‐facial excitatory and inhibitory responses in perioral muscles in hemifacial spasm (HFS). We examined 15 patients affected with idiopathic HFS and 8 healthy controls. Five patients had spasms mostly limited to the periocular region and 10 had spasms also involving the perioral muscles. Responses were recorded from the resting orbicularis oculi (OOc), levator labii superioris (LLS) and orbicularis oris (OOr) muscles, after supraorbital (SO) nerve stimulation and during isolated voluntary contraction of LLS muscle. Eight patients showed complete or partial preservation of the late silent period (SP2) in activated LLS muscle. The remaining 7 patients showed absence of SP2. Early and late excitatory responses were variably present in LLS muscle at rest. Patients with HFS clinically restricted to periocular muscles had at least partial preservation of the SP2. In conclusion, in HFS patients inhibitory trigemino‐facial reflexes are impaired and excitatory trigemino‐facial responses are elicited in perioral muscles. These two phenomena seem to develop independently; the degree of trigemino‐facial reflex impairment parallels the extension of involuntary movements to the lower facial muscles.