Hereditary spastic paraplegia

We report the first case of paroxysmal kinesigenic dyskinesia (PKD) with spastic paraparesis. A 17-year-old male began to show a dystonic posture in both his upper limbs when walking at age 12 years. Neurological examination revealed bilateral talipes cavus, spasticity in all extremities with general hyperreflexia and pathological reflexes. On starting to walk, he showed a dystonic posture in bilateral maniphalanx, wrists, elbows, and toes. Magnetic resonance imaging (MRI) revealed high T2-weighted signal intensity in bilateral pyramidal tract. Although the combination of pyramidal and the basal ganglia disorders is very rare, the present case suggests an inter-relation of the pyramidal and the basal ganglia systems. [Neurol Res 2002; 24: 684-686]

Keywords: Paroxysmal kinesigenic Dyskinesia; spastic paraparesis

INTRODUCTION

Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by episodic chorea, dystonia or other involuntary movements and postures that are brought on or exacerbated by voluntary movement, stress, or excitement1-3. To our knowledge, previous reports described cases with spastic paraparesis with dystonia, athetosis4 or paroxysmal nonkinesigenic dyskinesia (PNKD)5. However, there is no case report of PKD with spastic paraparesis. We here report the first case of a young man who showed PKD and spastic paraparesis.

CASE REPORT

A 12-year-old male started to develop a dystonic posture in both his upper limbs on running. At age 14, he occasionally felt difficulty at the beginning of a walk because his toes and upper limbs dystonically turned inward. He had to rest for about 10 sec, and then resuming walking. At age 17, his symptoms became frequent, making him unable to walk without periodically resting. He was admitted to our hospital.

He weighed 79 kg and was 173 cm tall. His father and paternal grandfather showed spasticity in all extremities (lower> upper extremities) with hyperreflexia, but they did not show a dystonic posture. On general physical examination, he was normal except for bilateral talipes cavus (Figure IB). On neurological examination, cranial nerves were intact, and dysarthria or corticobulbar dysfunction were absent. He showed spasticity in all extremities (lower > upper extremities). The deep tendon reflexes were hyperactive at both upper and lower limbs. A jaw jerk was present. Hoffmann's reflex was present bilaterally. Babinski's response was absent. On starting to walk, he showed a dystonic posture in bilateral maniphalanx, wrists, elbows, and toes (Figure IA). There were no other triggers such as alcohol, coffee, tea or emotions. He had no urinary incontinence. He showed no lower motor signs such as atrophy or fasciculation.

Blood laboratory tests and cerebrospinal fluid studies were all normal. He had normal or negative studies for HTLF-1 and syphilis serology. WAIS-R test showed total IQ of 86, and KWCST suggested a slight damage of frontal lobe. WMS-R showed damage of memory system. Distal motor and sensory conduction velocity were normal, but H/M-waves fraction were increased in bilateral lower extremities. Needle electromyography (EMG) and motor evoked potentials were normal. Auditory brainstem response (ABR) showed an extension of bilateral HI-V interpeak latency, and somatosensory evoked potentials (SEP) were also extensive in bilateral spinal conduction time. Surface EMG showed a synchronous activity in bilateral upper extremities, but not reciprocal (Figure1C), compatible to dystonia. Electroencephalography (EEG) showed no particular findings. MRI of the head presented a slight atrophy of the frontal lobe and a high signal intensity in bilateral pyramidal tract with T2-weighted image (WI) (Figure ID, arrows). Single photon emission computed tomography (SPECT) revealed normal cerebral circulation.

As a result, we considered this as a case of a severe PKD with slight spastic paraparesis. Frequency and the magnitude of PKD improved with daily 300 mg of carbamazepin for PKD, but spastic paraparesis did not change.

DISCUSSION

Paroxysmal kinesigenic choreoathetosis (PKC) is a term used to describe one of the paroxysmal dyskinesias, and is a relatively rare neurological condition which is characterised by sudden, brief attacks of involuntary movements which are precipitated by sudden voluntary movement. The nonkinesigenic form is historically termed paroxysmal dystonic choreoathetosis (PDC) and refers simply to attacks which are not provoked by sudden movement. Most cases of PKC, PDC and the intermediate form would fall under the PKD, PNKD, and paroxysmal exercise induced dyskinesia (PED) labels, respectively1,6. Demirkiran and jankovic' provide a classification system that divides the paroxysmal dyskinesias into four categories: PKD, PNKD, PED, and paroxysmal hypnogenic dyskinesias. PKD is a rare autosomal dominant (AD) disorder characterized by episodic chorea, dystonia or other involuntary movements and postures that are brought on or exacerbated by voluntary movement, stress, or excitement. PKD also occurs as a sporadic form. The abnormal movements typically begin at age 6-16 years, and boys are more commonly affected. PKD responds to anticonvulsant drugs such as carbamazepin or phenytoin2,3.

Our case showed a dystonic posture on starting to walk with onset of age 12. Dystonic posture of our case responded to carbamazepin. Our case also showed a spasticity in all extremities, spastic gait, general hyperreflexia with pathological reflexes. The differential diagnosis includes primary lateral sclerosis (PLS), HTLF-1 associated myelopathy (HAM) and hereditary spastic paraplegia (HSP). High signal intensity lesion in bilateral pyramidal tract (Figure iD) supports a Waller degeneration of upper motor neurons 8. The juvenile onset and lack of pseudobulbar dysfunction would be very unusual in PLS. His father and paternal grandfather showed spasticity in all extremities with hyperreflexia, but they did not show a dystonic posture. Thus, the spastic paraparesis of the present case would be AD inheritance, but PKD could be sporadic, or PKD in this case might also be dominantly inherited with low penetrance. He was compatible with PKD with complicated hereditary spastic paraparesis.

Complicated forms of spastic paraparesis with dystonic, athetosis4, or PNKD5 have been reported. PKD with spastic paraparesis had never been reported before the present case9. Though the etiology of PKD with spastic paraparesis is not clear, we speculate that this unusual combination between PKD and pyramidal disease was not merely a coincidence, but possibly a unique subtype of multisystem degeneration. There are two main theories about pathophysiology of PKD; epilepsy involving the thalamus or the basal ganglia and extrapyramidal disease involving the basal ganglia 10,11. We speculate that our case is a multiple system degeneration overlapping the basal ganglia and pyramidal disorders.

ACKNOWLEDGMENTS

This work was partly supported by Grant-in-Aid for Scientific Research (B) 12470141, (C) 13670649 and (Hoga) 12877211 from the Ministry of Education, Science, Culture and Sports of Japan, Kobayashi Magobe Memorial Medical Foundation, and by grants (Tashiro K, Itoyama Y, and Tsuji S), and Comprehensive Research on Aging and Health (H11 Choju-010, No. 207, Koizumi A) from the Ministry of Health and Welfare of Japan.

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Y. Ohta, Y. Manabe, C. Sasaki, M. Shiote, T. Hayashi, M. Shoji and K. Abe

Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan

Correspondence and reprint requests to: Yasuhiro Manabe, Depart ment of Neurology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. [manabe@cc.okayama-u.ac.jp] Accepted for publication May 2002.

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