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Foix–Chavany–Marie syndrome (FCMS) is characterised clinically by automatic voluntary dissociation of orofacial motility. It is caused by bilateral anterior opercular lesions and its aetiology is heterogeneous.1
Clinically, most cases of FCMS can be divided into three categories—developmental, acute/subacute, and transient.2 The most common cause of the developmental form is congenital bilateral anterior opercular dysplasia. The acute/subacute form is usually caused by infection in the CNS or cerebrovascular disease. The underlying pathogenesis of transient form is epilepsy. Rare variant cases of FCMS presenting with a slowly progressive clinical course have also been reported.3 We describe the clinical features of a patient with adult onset, slowly progressive FCMS, thought to be associated with chronic herpes simplex encephalitis.
A 29 year old Japanese woman developed epilepsy of generalised tonic-clonic type at the age of 15 and had been taking anticonvulsants for 14 years. She had had a normal pregnancy and delivery. Developmental assessment during schooling showed normal motor and psychological ability.
At the age of 27, she presented with dysarthria and dysphagia, which deteriorated gradually during the following 18 months. She also had difficulty with fine movements of her right arm at the age of 29. On admission, her voluntary orofacial motility was disturbed bilaterally, while emotional and involuntary facial movements were well preserved. Movement of the pharynx was slightly disturbed and gag and pharyngeal reflexes were reduced. She had difficulty in moving her tongue laterally. The other cranial nerves were normal. There was no sensory deficit or weakness in the limbs. Deep tendon reflexes of her right arm were slightly increased and her plantar responses were flexor. Rapid alternating movements of the right arm showed some clumsiness. A full scale IQ on the Wechsler adult intelligence scale, revised (WAIS-R) was 80, with a verbal IQ of 85 and a performance IQ of 78. There was no similar disorder in her family members.
The concentration of IgG (7.9 mg/dl) and the IgG index (1.89) in the CSF were increased, while the protein level in the CSF (30 mg/l) and the cell count (2/mm3) were normal. IgG antibody titres for herpes simplex virus (HSV), measured by enzyme linked immunosorbent assay (ELISA) in the serum (64.6) and CSF (6.4), were also raised. The serum to CSF ratio of the HSV IgG titre was decreased at 10.1, and the IgG index for HSV was increased at 3.28. IgM was negative. Polymerase chain reaction (PCR) methods did not reveal genomes for HSV 1 or 2 in the CSF. Antibodies to other virus were not detected and antibody testing for HIV was negative in the serum.
An EEG showed generalised mild slowing without paroxysmal activity. Magnetic resonance imaging (MRI) on FLAIR sequences revealed bilateral linear high intensity lesions in the rolandic area and severe atrophy of the operculum bilaterally, in addition to mild frontotemporal lobe atrophy (fig 1). These lesions on T1 weighted sequences showed no contrast enhancement after gadolinium administration. There was a partial defect in the body of the corpus callosum.
Treatment with acyclovir was begun but was suspended immediately because of a drug eruption. Treatment with intravenous vidarabine for 14 days was tried twice, and transient decreases of both IgG antibody titre and the IgG index for HSV in the CSF were observed on each occasion. There was no further deterioration in her neurological state after these treatments.
Neurological examination in our patient showed automatic voluntary dissociation of orofacial motility in addition to a disturbance of movement of the pharynx and tongue. An MRI study showed involvement of the opercular and rolandic regions bilaterally. This combination of clinical and neuroradiological features is typical of FCMS. However, our patient is unusual for two reasons. First, the clinical course of the FCMS was of adult onset and was slowly progressive; this type of deterioration has not been reported previously either in congenital dysplasia or in acquired acute/subacute CNS event such as stroke or infection.1 Although some cases with adult onset and a slowly progressive course have been reported, the aetiology of those cases remained obscure.3 Second, elevation of the IgG antibody titre and the IgG index for herpes simplex virus in the CSF showed the presence of chronic herpes simplex encephalitis. The temporal lobe is the favoured region for this. FCMS with an acute clinical course caused by herpes simplex encephalitis has been reported.4
Transient decreases in both IgG antibody titre and the IgG index for HSV after intravenous vidarabine were observed on both occasions the treatment was given. Although the correlation between increased IgG antibody for herpes simplex virus in the CSF and the chronic cerebral disturbance has not been verified, these observations support the view that chronic herpes simplex encephalitis remained active in our patient and could have been responsible for her neurological impairment. The clinical features—including the slowly progressive clinical course, the negative results of PCR testing for HSV, and the normal protein level and the cell count in the CSF—suggest that herpes simplex encephalitis was not the direct cause of the damage in the affected region. It is possible that persistent HSV infection may induce inappropriate activation of the immune system, resulting in neurocytotoxity because of cross reactivity.
Our patient had both a partial defect of the corpus callosum and epilepsy. This combination is often observed in patients with congenital cerebral dysplasia. However, the onset of developmental FCMS is always in the early infant period and is usually associated with delayed psychomotor milestones or mental retardation.5 Thus the pathogenesis in our patient is very unlikely to be explained on the basis of simple congenital dysplasia. The association between a partial defect of the corpus callosum and epilepsy in FCMS could be explained by the presence of herpes simplex virus infection dating from the fetal period. Although a necropsy proven case of FCMS that was probably caused by chronic herpes simplex encephalitis has been reported before,2 the clinical course in that case was not slowly progressive. In fact there have been no previous reports of slowly progressive FCMS associated with chronic viral infection.
In conclusion, this is the first report of a case of FCMS associated with chronic herpes simplex encephalitis. Further similar cases would establish this as a variant type of FCMS.