Itat. J. Neurol. Sci. 13:793-796, 1992

Associated polyneuropathy and demyelinating disease. Case report Rebaudengo N., Bianco C., Ferrero P., Troni W., Bergamasco B. Dipartimento di Neurologia, Universitg~ di Torino

We report a case in which an acute Guillain-Barrd-like sYndrome was quickly followed by a central demyelinating disease, documented by the clinical findings as well as by magnetic resonance imaging (MRI), electrophysiological and cerebrospinal fluid examinations. The close follow-on of the clinical signs seems to exclude a simple coincidence of two separate diseases and it may constitute further evidence for a possible etiological link between central and peripheral myelin damage. We discuss the possibility of a common pathogenic factor underlying central and peripheral demyelination.

Key Words: Polyneuropathy - - demyelinating disease

Introduction The clinical manifestations of multiple sclerosis (MS) are protean because of the varying location and extent of the foci of demyelination, generally confined to the central nervous system (CNS). The combination of MS and Peripheral Neuropathy is very unusual. The unsolved question is whether this association is coincidental or not. Also, demyelinating lesions may be present in both the central and the peripheral nervous system (PNS) as a primary inflammatory attack against myelin, or peripheral neuropathy could be determinated by secondary myelin damage in connection with joint degeneration, malnutrition and vitamin deficiency [4, 11]. We describe a case in which an acute demyelinating polyneuropathy was quickly followed by a central demyelinating disease, their close temporal link suggesting a possible causal relationship.

Case report This 17 year old man had been well until five months previously, when he experienced blurring of vision, particularly in the left eye, which was diagnosed by the ophthalmologist as papillitis. In June he developed paresthesias, numbness and Received 25 February 1992 - Accepted 30 June 1992

weakness in both upper and lower extremities, heaviness of the legs on exertion, and his walking rapidly deteriorated. He was hospitalized in an other neurological unit, where the reported neurological examination revealed the absence of all tendon reflexes and the absence of vibration and position sense from the waist downwards. Routine laboratory tests showed no abnormalities. The cerebrospinal fluid (CSF) contained a raised total protein (100 mg/100 ml), increased albumin concentration but there was no oligoclonal pattern of globulin bands. The electromyographic examina tion showed a diffuse marked reduction of motor conduction velocity (about 50% of normal lower values), indicating peripheral nerve demyelination, The symptoms, clinical signs and laboratory tests suggested an acute Guillain-Barr6 Syndrome. Both sensory and motor symptoms gradually improved and one month later the patient was discharged. He was well for nearly 60 days and then began again to suffer from weakness of both lower extremities. At the end of September he was admitted to our department for gait disturbances. At this time the abnormal neurological findings were: bilateral optic pallor, mild weakness in both lower extremities, absent abdominal reflexes, bi lateral plantar extensor responses, hyperactive deep tendon reflexes of the lower limbs, particularly the knee jerk, with areflexia of the upper limbs. He 793

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Fig. I. Series ~1' Magnetic Re.~on~tnc'e ~cans ./J'om our patient illustrating several white matter lesions ilt the CNS.

matter and of the white matter in other areas of the cerebral hemispheres and brainstem (Fig. t). Brainstem auditory evoked potentials (BEAPs) and checkerboard reversal pattern visual evoked potentials (VEPs) were abnormal on both the left and the right side (Fig. 2). BAEPs showed prolonged interpeak latencies associated to morphological abnormalities of wave V. Similarly, the VEPs showed prolonged latencies of the major positive P100 component associated to morphological alterations, with inconstant shape reproducibility in serial recordings. Motor conduction velocity was still significantly reduced over all segments of the nerves in the upper and the lower extremities (median: 35.8 m/sec on the right side, 40.4 m/sec on the left side; ulnar: 44 m/sec on the right side, 32.7 m/sec on the left side; peroneal: 43 m/sec on the right side). No sensory potentials could be recorded for the median, ulnar or sural nerves on either side. The clinical signs and laboratory findings point strongly to coexistence of a multifocal central and diffuse peripheral involvement of the nervous system. Prednisone 50 mg daily was tried and the patient showed progressive improvement in the following two weeks. A month later, hyperreflexia of the lower limbs was significantly reduced and also segmental motility and ataxia were getting better. At the end of November 1990, the patient again underwent neurological examination. His walking had recovered almost completely, apart from a slight ataxia. All the deep tendon reflexes were normally active; the upper abdominal reflexes were normal, whereas the lower ones were absent. The muscles of the lower extremities were slightly atrophic and vibration and position senses were still reduced in the legs. Discussion

suffered from episodes of slurred speech, ataxia (on closing his eyes), subjective vertigo and blurring of vision. Sensory e x a m i n a t i o n revealed complete loss of vibration sense in the legs and mild impairment of superficial sensation. Routine laboratory tests showed no abnormalities. The CSF contained a raised total protein (98 mg/100 ml), increased IgG (12.1 mg/dl) and albumin (106 mg/ all) concentrations, normal IgG Index (value: 0.57) [7], raised CSF/serum albumin rate (value: 21.5, normal upper limit: 8), raised "de novo" IgG Synthesis Rate (value: 10.6, normal upper limit: 3.3) [16] and an oligoclonal globulin banding. MRI revealed many cerebral lesions in the T2weighted images, of the periventricular white 794

The clinical features of this patient seem to indicate that he had suffered from acute inflammatory demyelination of the PNS just four months before the occurrence of a multifocal involvement of the CNS. However, it cannot be excluded that the real onset of the disease was a central demyelinating episode, as suggested by the reported visual disturbances consistent with an optic neuritis. Unfortunately MRI examination was not available during the former hospitalization at the onset of the disease. Anyway, whatever may be the temporal relation between the central and peripheral episodes, it seems reasanable to suppose a common etiological denominator, as suggested by their close occurrence. Such an association was first described by Wartenberg [18], who reviewed the literature on polyneuritis and MS to that time. Several authors [2, 5, 10, 13, 17, 18] discussed the concomitance between CNS and PNS myelin affection. Schoene et al. [15] had suggested the

Rebaudengo N.: Polyneuropathy and dernyelinating disease

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possibilty of a common pathogenesis and described a case in which there was sensitivity both to CNS myelin basic and to PNS antigen. The evidence for a primary inflammatory segmental demyelination was based on the occurrence of onion bulb neuropathies in the nerve roots and peripheral nerves, observed in patients with MS. Morris and Young [9] suggested a possible relationship between the etiological factors in GBS and MS, presenting five cases of MS with onsets closely related to swine influenza vaccination. Lassman et al. [6] described a case of simultaneous acute inflammatory demyelination in the CNS and PNS in MS. In addition, the evidence of a possible common pathogenic factor was supported by the frequent cross-reactivity of CNS and PNS myelin antigens in experimental allergic encephalomyelitis (EAE) [8, 19]. Several cases have already been reported in which central demyeli-

Fig. 2. Evoked potential alterations in our patient. Above: Transient black/white checkerboard VEPs on stimulation of the left eye (with contralateral masking). Filters 0.5-160 Hz, interstimulus interval (ISI) 0.5 sec. Visual angle 50" Luminance 20 cd. Contrast 50%. Surface AgCl cup electrodes Oz-C=. Two series of 100 averaged stimuli. Below: BAEPs tb' monaurtd click stimulation off the left ear, with contralateral masking by white noise. Filters 53-160(J Hz. Stimulus intensity 75 dB HL. IS1 0.10 msec. 7~wo series of 2000 averaged stimuli. Surface AgCl cup electrodes Cz-mastoid. The figure shows both ipsilateral and contralateral responses, b7 both visual and auditory evoked responses there is evMence of the alterations reported in the text.

. . . .

nating lesions and inflammatory polyneuritis occurred on clearly separate occasions [1, 3, 12, 14]. In some cases, a few years passed between the two events, in other cases the patients developed acute Guillain-Barr6 Syndrome after MS had been diagnosed. We emphasize the temporal connexion between the two immunological impairments in our patient and underline the very short time that elapsed between the two onsets. The relevance of our case to the general problem of the etiology of MS is unclear. The appearance of oligoclonal bands in the second sample of CSF after being absent in the first suggests that in our case the initial exogeneous factor may have primed an intrathecal synthesis of imrnunoglobulins. This hypothesis will be strengthened, if our patient later presents CNS demyelinating signs with a relapsing-remitting course.

Sommario Viene presentato un caso in cui a d una sindrome acuta tipo Guillain-Barrd ~ successivamente seguita una malattia demielinizzante centrale, come d o c u m e n t a t o dal quadro clinico, dalla Risonanza M a g n e tica Nucleare (RMN), dalle indagini elettrofisiologiche e liquorali. La particolare sequenza temporale della sintomatologia clinica sembra escludere una semplice coin-

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cidenza di due malattie distinte e sembra costituire una ulteriore p r o v a di un possibile legame ezioIogico tra un danno mielinico centrale e periferico. Viene discussa la possibilitd che un comune f a t t o r e p a t o g e n e t i c o p o s s a essere responsabile di demielinizzazione centrale e periferica.

Address reprint requests to: Dr. W a l t e r Troni Clinica Neurologica Via Cherasco, 15 - 10126 Torino

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[11] REYNOLDS E.H., LINNEL J.C., FALUDY J.E.: Multiple sclerosis associated with vitamin B12 deficiency. Arch. Neurol. 48:(8), 808-811, 1991. [12] Ro Y.I., ALEXANDER B,, OH S.J.: Multiple Sclerosis and hypertrophic demyelinating peripheral neuropathy. Muscle Nerve, 6:312-316, 1983. [13] ROSEMBLUM W.I., BUDZILOVlCH G., FEmIN I.: Lesions o f the spinal cord in polyradiculoneuropathy o f unknown aetiology and a possible relationship with the Guillain-Barrg syndrome. J. Neurol. Neurosurg. Psychiatry, 29:69-76, 1966. [14] SANDERS E.A.C.M., LEE K.D.: Acute GuillainBarr( syndrome in Multiple Sclerosis. J. Neurol., 234:128, 1987. [15] SCHOENE W.C., CARPENTER S., BEHAN P.O., GESHWlND N.: "'Onion bulb" formation in the central and peripheral nervous system in association with Multiple Sclerosis and hypertrophic polyneuropathy. Brain, 100:755-773, 1977. [16] TOURTELOTTEW.W., MA B.I.: Multiple Sclerosis: the blood-brain barrier and the measurement of de novo central nervous system lgG synthesis. Neurology, 28 (2):76-83, 1978. [17] UNCINI A., GALLUCO M., LUGARESl A. ET AL.: CNS involvement in chronic inflammator)' demyelinating polineuropathy: an electrophysiological and MR1 study. EMG Clin. Neurophysiol., 31 (6):365-371, 1991. [18] WARTENBERG R., Neuritis, sensor3, neuritis, neuralgia: a clinical study with review of the literature, Oxford University Press, New York, 296-305, 1958. [19] WISNIEWSKI H.M., PRNEAS J., RAINE C.S.: An ultrastructural stud)' of experimental encephalomyelitis in the peripheral nervous system. Lab. Invest., 21:105-118, 1969.