Correspondence Address: Dr. Abhilekh Srivastava Department of Neurology, GB Pant Hospital, New Delhi 110002 India
Source of Support: None, Conflict of Interest: None
Neuropathic tremors are often encountered in both hereditary as well as acquired inflammatory demyelinating neuropathies, such as IgM paraproteinemic neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy and occasionally during the recovery phase of Guillain-Barré syndrome (GBS). Acute motor axonal neuropathy (AMAN) accounts for up to 30–65% the patients with GBS in East Asia and is rarely associated with a neuropathic tremor. We report a patient with AMAN, who presented with pure motor quadriplegia with bulbar symptoms and a prominent atypical resting head tremor during the acute phase of illness, which showed an excellent response to topiramate therapy.
Keywords: GBS, head tremor, neuropathic tremor
How to cite this article: Khwaja GA, Srivastava A, Chaudhary N, Chowdhury D. Topiramate Responsive Prominent Head Tremor as an Atypical Presentation of Guillain-Barré Syndrome. MAMC J Med Sci 2018;4:93-5
How to cite this URL: Khwaja GA, Srivastava A, Chaudhary N, Chowdhury D. Topiramate Responsive Prominent Head Tremor as an Atypical Presentation of Guillain-Barré Syndrome. MAMC J Med Sci [serial online] 2018 [cited 2021 Sep 16];4:93-5. Available from: https://www.mamcjms.in/text.asp?2018/4/2/93/239997
Neuropathic tremors are more common in demyelinating neuropathies and are only rarely encountered in axonal neuropathies. Action-postural neuropathic hand tremors have been only occasionally reported during the recovery phase of acute inflammatory demyelinating polyneuropathy (AIDP)—the demyelinating subtype of Guillain-Barré syndrome (GBS). We report a rare case of topiramate responsive prominent head tremor as an atypical presentation of acute motor axonal neuropathy (AMAN)—the axonal subtype of GBS.
An 18-year-old female presented to us with a 1-month history of acute onset, rapidly progressive ascending weakness in all the four limbs that evolved to complete quadriplegia over a period of 5 days. The motor weakness was accompanied by severe dysphagia and anarthria but without any facial weakness or ocular involvement. She had also developed a severe, continuous disabling head tremor that was extremely distressing and subsided only during sleep. There was no history of any sensory loss, respiratory distress, or bladder–bowel disturbance, and the weakness had remained static over the last 3 weeks. There was a history of a short febrile illness lasting for around 3 days about 1 week prior to the onset of motor weakness.
On examination, the patient was fully conscious and alert. Her comprehension was intact, but there was complete anarthria. Her vitals were stable, and both general physical and systemic examinations were normal. On ocular examination, fundus, pupil size, reaction to light, and ocular movements were normal, and there was no nystagmus. There was no weakness or a loss of sensation on the face. On bulbar testing, palatal movements were decreased, and gag reflex was bilaterally absent; however, tongue movements were preserved. There was a flaccid quadriplegia with a mild wasting of all the four limbs with areflexia and mute plantars. Neck and truncal weakness was also present, but sensations were intact. A continuous head tremor, both in the yes–yes and no–no directions (Video 1—1st part), was also observed. The tremor increased during emotional stress and while attempting to raise the head.
On investigation, complete blood count, blood sugar, serum electrolytes, blood gases, and kidney and liver function tests were normal. She tested negative for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg), and anti-Hepatitis C virus (HCV). Urine testing was negative for porphobilinogen. An autoimmune panel for antinuclear antibody (ANA), other nuclear antigens, and anti-antiganglioside antibody (GQ1B) antibodies was negative. Results of X-ray chest, electrocardiogram (ECG), echocardiogram, and magnetic resonance imaging (MRI) brain and spine were normal. Cerebrospinal fluid (CSF) examination revealed albumin-cytological dissociation with no cells and a protein level of 120 mg/dl. A nerve conduction study revealed a pure motor axonal pattern of polyneuropathy.
In view of a history of acute onset pure motor quadriplegia with bulbar symptoms and the electrophysiological evidence of an axonal neuropathy, a diagnosis of AMAN subtype of GBS with a prominent head tremor as an atypical presentation was made. Because her illness had evolved over a week and had not progressed over the last 1 month, she was not given intravenous immunoglobulins (IVIG) and received symptomatic treatment only. The head tremor showed no response to either propranolol or gabapentin, which were tried initially. A subsequent trial of topiramate gave an excellent response with a near complete subsidence of the head tremor on a dose of 200 mg/day (Video 1—2nd part). Over the next 1 month, a gradual improvement in her motor power and bulbar symptoms was also observed. She began to accept orally, her Ryle’s tube was removed, and she started vocalizing as well. Around 1 month after a complete subsidence of the head tremor, topiramate was slowly tapered off, with no recurrence of the tremor. On a 3-month follow-up post discharge, her speech was near normal, but motor power was around grade 2–3 in the limbs.
GBS is an acute onset immune-mediated, inflammatory polyradiculoneuropathy, which classically presents as a rapidly progressive pure motor quadriparesis. First described from France in 1916, GBS was initially regarded as a purely demyelinating neuropathy. In 1991, however, a pure motor axonal subtype of GBS was identified from China and named as Chinese paralytic syndrome or “acute motor axonal neuropathy” or AMAN. Ever since the recognition of various demyelinating and axonal subtypes of GBS, the classical demyelinating subtype is now labeled as “acute inflammatory demyelinating polyradiculoneuropathy or AIDP.”
AMAN accounts for up to 30–65% of patients with GBS in East Asia (China and Japan) and the developing countries of Central and South America., It is frequently associated with Campylobacter jejuni enteritis, and the molecular mimicry of peripheral nerve gangliosides to the bacteria is believed to be the underlying pathophysiological basis of AMAN. AIDP, on the other hand, is more frequently associated with Cytomegalo and Epstein-Barr virus infections. On electrophysiology, a demyelinating pattern is observed in AIDP, but in AMAN, motor nerve conduction velocities are preserved with a reduced amplitude of the compound muscle action potential, indicating an axonal pattern of neuropathy. A similar pattern was also recorded in our patient, thereby confirming the diagnosis of AMAN. In contrast to AIDP, a dysfunction of the cranial nerves and autonomic nerves is less frequent in AMAN, and the tendon reflexes may be preserved or even be hyper-reflexic. Due to extensive axonal degeneration, recovery in AMAN can at times be slow or even poor as compared to the demyelinating subtype.
Tremor is a hyperkinetic movement disorder characterized by the rhythmic oscillations of one or more body parts. Neuropathic tremor was first described in the Roussy–Lévy syndrome, an autosomal dominant (AD) form of demyelinating hereditary neuropathy. Acquired inflammatory peripheral neuropathies, especially of the demyelinating type can also be accompanied by a neuropathic tremor.
Among the inflammatory neuropathies, tremor is most frequent in IgM paraproteinemic neuropathy (IgMPN) and has been reported in up to 80% of these cases. In a study of 43 patients with inflammatory neuropathies, Saifee et al. reported hand tremors in around 58% of the patients with chronic inflammatory demyelinating polyradiculoneuropathy and 56% of the patients with multifocal motor neuropathy with conduction block. Action postural hand tremors have also been occasionally reported during the recovery phase of GBS. Grand’Maison et al. in their case series of 12 patients with recurrent GBS detected a neuropathic hand tremor in two patients only. In one of these patients, the tremor affected the legs and head also, though to a lesser degree.
The origin of the neuropathic tremor is unclear. It may be attributed to either a cerebellar dysfunction or a disturbed feedback in the nerve reflex arc due to the peripheral slowing and distortion of the afferent nerve signals. Neuropathic tremors predominantly affect the arm and hand muscles and are mostly postural and kinetic in nature with a frequency of 3–6 Hz. The tremor can be severely disabling and at times interfere with the activities of daily living. In our case, a continuous, severe, and distressing resting head tremor, both in the yes–yes and no–no directions, was encountered in the setting of a severe quadriplegia due to the axonal subtype of GBS or AMAN, which is quite rare. Even though a disabling neuropathic hand tremor in the setting of AMAN has been reported by Coltamai et al. as well, neuropathic tremors are extremely rare in axonal neuropathies. Moreover, another unusual feature of our patient was that the tremor evolved during the acute rather than the recovery phase of the illness and was confined to the head only. It, however, showed a good response to short-term topiramate therapy without any recurrence after drug withdrawal. Motor recovery was, however, slow, and at a 3-month follow-up, power in the limbs had improved to grade 2–3/5 only, reflecting the axonal nature of the neuropathy. To the best of our knowledge, this is the first case report of an isolated neuropathic head tremor in AMAN.
The treatment of neuropathic tremor is difficult. A small number of patients may respond to immunomodulating therapy for the underlying neuropathy and rarely respond to medications, such as pregabalin, as reported by Coltamai et al. Our patient did not receive intravenous immunoglobulins (IVIg) or any form of immunomodulating therapy. Her head tremor did not respond to either gabapentin or propranolol, but it showed a dramatic response to topiramate. Topiramate is primarily an anticonvulsant that was discovered in 1979. It is also used for the management of primary headache disorders and essential tremor. It has a multimodal mechanism of action that includes the blockade of voltage-dependent sodium channels, the potentiation of GABAergic transmission, and the inhibition of excitatory pathways through an action at AMPA receptor sites. It is also a weak carbonic anhydrase inhibitor, and common side effects include weight loss, paresthesia, poor concentration, memory disturbance, and an increased risk for glaucoma and kidney stones. Besides essential tremor, topiramate may also have a role in the treatment of neuropathic tremor, as was observed in our patient. However, till date, there have been no documented trials of its use in this setting. In conclusion, the present case highlights that even the axonal variants of GBS such as AMAN can be associated with an atypical neuropathic head tremor. Topiramate emerges as an effective treatment option for neuropathic tremor in patients who fail to respond to conventional agents such as propranolol and gabapentin.
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The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Ho TW, Mishu B, Li CY, Gao CY, Cornblath DR, Griffin JW et al. Guillain-Barré syndrome in northern China: Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 1995;118:597-605.
Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N. Axonal Guillain-Barré syndrome: Relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan. Ann Neurol 2000;48:624-31.
Visser LH, van der Meché FG, Meulstee J, Rothbarth PP, Jacobs BC, Schmitz PI et al. Cytomegalovirus infection and Guillain–Barré syndrome: The clinical, electrophysiologic, and prognostic features. Neurology 1996;47:668-73.