Pyramidal Tract Deficits and Polyneuropathy in Hyperthyroidism

Combination Clinically Mimicking Amyotrophic Lateral Sclerosis

MELANIE FISHER, M.D. JOHN E. MATEER, M.D.” IRMA ULLRICH, M.D. JOSE A. GUTRECHT, M.D.+ Morgantown, West Virginia

From the Departments of Medicine and Neurology, West Virginia University, Morgantown, West Vir- ginia. Requests for reprints should be addressed to Dr. Melanie Fisher, Department of Medicine, West Virginia University Hospital, Morgantown, West Virginia 26506. Manuscript accepted June 15, 1964. l Current address: Department of Neurology, Geisinger Medical Center, Danville, Pennsylvania 17622. 7 Current address: Lahey Clinic, Burlington, Massachusetts 01805.

Generalized weakness, intermittent dysphagia, and a 40-pound weight loss developed in an elderly man over a six-month period. Examination revealed weakness, atrophy and fasciculations of extremity musculature, pseudobulbar speech, hyperactive upper extremity reflexes, and extensor toe signs without sensory loss. Results of electrodiagnostic studies were consistent with an axonal polyneuropathy. Endocrlnologic results were compatible with hy perthyroidism. Radioiodine therapy resulted in resolution of clinical neurologic symptoms and signs within seven months. This case il- lustrates a previously undescribed concurrence of hyperthyroid associated polyneuropathy and pyramidal tract dysfunction that led to an initial clinical diagnosis of amyotrophic lateral sclerosis.

Hyperthyroidism may be associated or present with a variety of neu- romuscular disorders, most commonly a proximal myopathy [ 1,2]. Peripheral nerve involvement in hyperthyroidism is uncommon [2-71, and the association of the two disorders is believed by some [7] to be questionable. Rarely, reversible pyramidal tract dysfunction [ 2,8- 101 is associated with thyrotoxic states.

We report herein the case of a man presenting with a constellation of upper and lower motor neuron signs clinically suggesting amyo- trophic lateral sclerosis. Electrodiagnostic studies indicated an axonal polyneuropathy rather than motor neuron disease. Chemical hyper- thyroidism was subsequently detected. Radioiodine treatment resulted in resolution of this upper motor neuron disorder and progressive improvement in the neuropathy. To our knowledge, this represents the first reported case in which these two uncommon neurologic manifestations of hyperthyroidism have been documented to appear concurrently.

CASE REPORT

A 69-year-old white man was admitted to the West Virginia University Hospital for evaluation of progressive weakness and a gait disturbance. Six months prior to admission, he noted the onset of generalized weakness and a “staggering gait.” He reported mild dysphagia with intermittent nasal regurgitation of fluids. “Slurrad” speech was reported by the family. Despite an excellent appetite, he progressively lost 40 pounds in weight. He denied headaches, diplopia, cramps, paresthesia% radicular pain, and bladder or bowel dysfunction. The family history was negative for neurologic and en- docrine disorders. Past medical history revealed no toxic exposure or ethanol use.

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TABLE I Conduction Studies

Normal Values

Motor Right Median

Velocity (m/riec) 48-70 Distal latency (msec) 2.4-4.6 Amplitude (mv) 8.0-15.0

Right Ulnar Velocity (mlsec) 45-75 Distal latency (msec) 1.8-4.2 Amplitude (mv) 5.6-15.0

Right Peroneal Velocity (mlsec) 38-65 Distal latency (msec) 3.4-6.8 Amplitude (mv) 3.5-10.0

Sensory Right Median

Distal latency (msec) 2.8-3.7 Amplitude (pv) >lO

Right Ulnar Distal latency (msec) 2.1-3.2 Amplitude (pv) >lO

Pallent’s Values 2ltll90 4/29109 9/24/M

47 45 48 5.1 4.9 4.5 3.0 6.0 5.0

46 46 47 3.1 3.0 2.5 3.6 6.0 4.5

37 37 36 4.6 4.0 4.0 0.1 0.1 1.5

NR NR NR NR NR NR

NR NR NR NR NR NR

NR = no response.

The patient was alert and oriented. His speech was nasal and occasionally explosive. No emotional incontinence was noted. Resting pulse on numerous occasions was 80 to 90 per minute. No palpable thyroid enlargement was found. Mild bilateral masseter and tongue weakness were present. A neurologic consultant noted scattered fasciculations of the tongue. The gait was slow and mildly spastic. A fine tremor of the hands was present. Deep tendon reflexes were brisk and symmetric in the upper extremities and normal in the lower extremities. Abdominal reflexes were absent. The jaw jerk was slightly increased. Muscular tone was normal. A left extensor toe sign was present. The right toe sign was equi- vocally extensor. Mild atrophy and moderate (grade Ill to V) weakness of all muscular groups was evident, most promi- nent distally. Fasciculations were present in intrinsic hand, forearm, and quadriceps muscles. No percussion myoedema was detected. Sensation, tested by several examiners, was normal to vibration, touch, position, and pinprick modali- ties.

Complete blood cell count, electrolyte, glucose, calcium, phosphorus, albumin, serum glutamic oxaloacetic trans- aminase, lactate dehydrogenase, and creatine phosphokinase values, and results of chest radiography were normal. Elec- trocardiography revealed normal sinus rhythm at 85 beats per minute. Cervical spine film demonstrated moderate de- generative changes, most marked at cervical vertebral levels 5 to 8 and 8 to 7. Initial nerve conduction studies (Table I) were characterized by unobtainable sensory nerve action potentials, minor slowing of motor vehfcles, and mildly de- pressed amplitudes of evoked compound muscle action potentials. Repetitive stimulation of two nerves revealed no

decremental or facilitatory responses before and after ex- ercise. Electromyography revealed low-grade fibrillations and occasional fasciculations in upper and lower extremity muscles, being most prominent distally. Motor unit potentials were large in amplitude, moderately complex and polyphasic in configuration, and reduced in number on maximal con- traction. Biopsy of the left biceps brachii revealed mild neurogenic atrophy. This was characterized by variation in fiber size, angularity and atrophy of both fiber types, a ten- dency for type II-A fiber grouping, and increased nonspecific esterase activity (Flgure 1) in atrophic fibers.

The serum thyroxine level was initially 11.0 pg/dl. On re- peated determination, it was 15.0 (normal 4.5 to 11.5 pg/dl). Triiodothyronine resin uptake was 53 percent (normal 25 to 35 percent). Technetium scanning revealed a diffusely en- larged thyroid. Iodine 131 uptake was 48 percent (normal 10 to 30 percent).

Propranolol, 20 mg four times per day, produced a de- crease in the clinical tremor. Ten mCi of iodine 131 was administered. Over the ensuing three months, the patient gained 25 pounds. His gait returned to normal, extensor toe signs became flexor, dysphagia resolved, and his speech returned to normal. Extremity strength improved more slowly but was believed to be nearly normal seven months after treatment.

COMMENTS

The clinical combination of upper motor and lower motor neuron signs in the present case led to an initial diagnosis of amyotrophic lateral sclerosis. Classic manifestations of hyperthyroidism were absent with the exception of a fine tremor. The tremor and the elec- trodiagnostic demonstration of a polyneuropathy, rather than motor neuron disease, prompted a search for a toxic or metabolic disorder. The subsequent diagnosis and treatment of hyperthyroidism resulted in dramatic and nearly complete neurologic recovery. We conclude that the hyperthyroid state was responsible for both major components of this man’s neurologic syn- drome.

In previously reported cases [8-lo] of pyramidal tract dysfunction in hyperthyroidism, spasticity, Babinski signs, hyper-reflexia, and spastic bladders were re- versible with treatment of the hyperthyroid state. Clinical evidence of lower motor neuron disease and electro- myographic abnormalities were absent. The patho- physiology is unknown.

Evidence for corticospinal tract dysfunction in our case was manifested by similar symptoms (with the exception of bladder dysfunction) and signs, in addition to a pseudobulbar speech pattern suggestive of con- comitant corticobulbar tract involvement. Both the corticospinal and corticobulbar dysfunction were re- versible with antithyroid therapy. The lack of hyper- reflexia in the lower extremities, despite the presence of Babinski signs, reflected the concomitant presence

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of a neuropathy, which was a feature unique to the present case.

The association of neuropathy with hyperthyroidism is quite rare and has been questioned [7]. Nevertheless, several studies [4-61 document both clinical and electrodiagnostic findings consistent with neuropathy in well-established cases of thyrotoxicosis. It has been suggested that severe hyperthyroidism-associated peripheral neuropathies may have been responsible for cases of Basedow’s paraplegia [6].

Neuropathy occurring in association with cortico- spinal tract signs has been previously reported in a case of thyrotoxicosis [3]. Unequivocal evidence of pe- ripheral nerve involvement in this case of posterolateral myelopathy, however, was not given. Motor conduction velocities were reported to have been “reduced,” sensory conduction studies were not mentioned, and electromyographic results were normal. None of these parameters was apparently evaluated after antithyroid therapy, and only mild clinical neurologic improvement was noted. Paradoxically brisk lower extremity reflexes were seen in several cases of documented thyrotoxic neuropathy reported by Ludin et al [4] but clear ex- tensor toe signs were absent.

The pathophysiologic basis for peripheral nerve disorders in hyperthyroidism is unknown. A lesion in- volving anterior horn cells has been postulated [5]. This is supported by relative preservation of motor nerve conduction velocities and normal sensory nerve con- duction parameters in the face of clearly neurogenic changes on electromyography [4,5]. Abnormal sensory and motor conduction parameters, however, have been reported in severe cases [6] of thyrotoxicity-associated neuropathy, suggesting a process involving either pe- ripheral segments of nerve or both the sensory ganglion and anterior horn cells.

Our patient had symptoms (weakness) and signs (atrophy and fasciculations) suggestive of a disorder involving anterior horn cells or their distal processes. Despite repeatedly normal results of sensory exami- nations, conduction studies revealed evidence of sen- sory nerve involvement as well. A sural nerve biopsy specimen was unfortunately not obtained. Electro- myographic features of the present case were clearly neurogenic [ 11,121 rather than myopathic. The proxi- mal muscle biopsy specimen also reflected neurogenic atrophy [ 131 rather than a myopathic process.

An axonal neuropathy appears to be the best ex- planation for the clinical and electrodiagnostic features of the present case. The minor slowing of nerve con- duction velocities, reduction in compound muscle action potential amplitudes, lack of impulse dispersion fol- lowing proximal stimulation, and absence of sensory nerve action potentials are electrodiagnostic features

Figure 1. Right biceps muscle biopsy specimen illustrating mildly atrophic fibers with increased esterase activity (single arrows); note the angular, severely atrophic fiber with marked esterase positivity (double arrows) (nonspecifiq esterase stain; original magnification X 480, reduced by 30 per- cent).

of a process involving anterior horn/dorsal root ganglion cells or distal axons rather than one involving peripheral myelin [ Ill. Fibrillations, fasciculations, large-ampli- tude polyphasic units, and a reduced recruitment pattern are also consistent with a subacute to chronic process involving either anterior horn cells or motor axons [ 121. We favor a thyrotoxicity-induced physiologic and structural dysfunction at the anterior horn/dorsal root ganglion cellular level to explain some of these features rather than a purely peripheral process.

The present case illustrates a unique combination of two rare neurologic manifestations of hyperthyroid- ism and provides further clinical and electromyographic documentation of the occurrence of thyrotoxic poly- neuropathy. It also reemphasizes the need for elec- trodiagnostic and metabolic evaluation in cases of suspected motor neuron disease.

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11. Asbury AK, Johnson PC: Metabolic and toxic poiyneuropathies. in: Pathology of peripheral nerve. Major problems in pa- thoiogy, voi 9. Philadelphia: WB Saunders, 1978; 72-96.

12. Daube JR: Needle examination in electromycqaphy. American Association for Electromyography and Eiectrodiagnosis minimonograph no. 1 I, 1979; l-92.

13. Karpati G: The principles of skeletal muscle histochemistry in neuromuscular diseases. in: Vinken PJ, Bruyn GW, Ringel SP, ed. Diseases of muscle, part I, voi 40. Handbook of clinical neurology. Amsterdam: Elsevier North Holland Biomedical Press, 1979; l-6 1.

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