Clinical Reasoning: A 58-year-old man with progressive ptosis and walking difficulty

Abstract

A 58-year-old man developed progressive walking difficulty over 10 years. He had normal development and an unremarkable birth history. At age 30, he developed bilateral drooping eyelids with double vision. At age 48, he developed progressive gait unsteadiness, slurred speech, and swallowing difficulty. At age 55, he needed to walk with a cane. He did not have seizures, hearing loss, or memory impairment. He did not have any history of alcohol abuse or exposures to anticonvulsants. His mother has congenital cardiac disease and diabetes mellitus, and his sister has had epilepsy since childhood. His daughter is healthy.On examination, the patient had left exotropia and bilateral ptosis without fatigability. His pupillary reflex to light was normal. He had partial horizontal gaze palsy and lack of upward gaze, which was not overcome by vestibulo-ocular reflex. His saccadic eye movements were slow without nystagmus or square wave jerks. He had scanning speech. He had normal muscle power but decreased vibratory sensation and proprioception in his legs, and his deep tendon reflexes were absent. He had mild bradykinesia and arm rigidity without rest tremor. He had mild dysmetria in bilateral finger-nose-finger, finger chase, and heel-shin slide examinations and he had impaired rapid alternating movements. He had wide-base gait with variable stride length but good heel strike, and he could not perform tandem gait (video at Neurology.org).

Ataxia

“…Several abnormalities of eye movements could be associated with different types of ataxia: (1) saccadic intrusion in fixed gaze (ie, square-wave jerks), which can be seen especially in Friedreich ataxia, 3 (2) horizontal or vertical end-gaze nystagmus, which occurs in many types of ataxia, among which down-beat nystagmus can often been seen in spinocerebellar ataxia (SCA) type 6 (SCA6), (3) hypometric or hypermetric saccades, which can be observed in many types of ataxia, (4) breakdown of smooth pursuit, often encountered in SCA3, 5 (5) slow saccades, typical for SCA2, 5 (6) ophthalmoplegia/ophthalmoparesis, which can be observed in sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), and (7) ptosis, which can occur in SANDO and ataxia associated with mitochondrial genome mutations. 6 Among these signs, nystagmus and hypometric or hypermetric saccades are commonly shared by ataxic disorders; therefore, these signs are helpful in differentiating cerebellar ataxia from sensory ataxia, especially in the early stages of the disease when no cerebellar atrophy is found on neuroimaging.…”

“…The age of onset is in adulthood with ophthalmoplegia, ptosis, myoclonus, and epilepsy. 6 Bilateral inferior olivary nucleus T2 hyperintensity could sometimes be observed on brain MRI (FIGURE 7-1F).…”

Ataxias: Hereditary, Acquired, and Reversible Etiologies

“…Since POLG mutations cause mitochondrial Ataxias: Hereditary, Acquired Lin, Kuo dysfunction, muscle biopsy in these patients shows mitochondrial proliferation. 235,236 Three ARCAs are commonly associated with oculomotor apraxia: ataxia telangiectasia (A-T), ataxia with oculomotor apraxia type 1, 2, and 4 (AOA1, AOA2, and AOA4). A-T is caused by mutation in ATM gene, which encodes a protein important for DNA repair.…”

“…Since POLG mutations cause mitochondrial dysfunction, muscle biopsy in these patients shows mitochondrial proliferation. 235 236…”

Ataxia in Neurometabolic Disorders

“…In addition, the clinical picture changes with the severity of the disease. The main anomalies include [ 11 , 83 , 84 , 85 ]: hyper- or hypometric saccades (observed in many types of ataxia); vertical or horizontal nystagmus (observed in many types of ataxia); saccadic intrusion in fixed gaze (i.e., square-wave jerks); breakdown of smooth pursuit; slow saccades; ophthalmoplegia/ophthalmoparesis, (observed in sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO)); ptosis (observed in SANDO and ataxia associated with mitochondrial genome mutations). …”