Whipple's disease presenting with segmental myoclonus and hypersomnia

Abstract

Whipple's disease is an infection by Tropheryma whipplei. Non-neurological manifestations include fever, diarrhea, weight loss, and seronegative migratory polyarthritis. 1 The central nervous system (CNS) follows the gastrointestinal tract as the second major site of involvement. Myoclonus and sleep disturbances due to hypothalamic involvement have been reported in 16% to 25% and 11% to 31% of patients with CNS Whipple's disease, respectively. However, they are rare as presenting symptoms. [2][3][4] We report the case of a 43-year-old Caucasian man who presented with a 2-year history of segmental myoclonus of the trunk and arms. These movements were unpredictable, not voluntarily suppressible, and persisted during sleep. They began in the right arm, and progressed to the trunk and left arm within a year. Initial examination revealed high amplitude, moderate velocity myoclonic movements of the arms and trunk, most prominent at rest and fully ablated with action. Initial investigations including electromyography (EMG), electroencephalography (EEG), and serological screening for Huntington's and Wilson's disease were unremarkable. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed mild cerebellar atrophy and C6-C7 degenerative disc disease with mild indentation of the thecal sac and no cord signal change. A low dose of clonazepam was started with symptomatic improvement of the myoclonus.A year later, he developed new attacks of hypersomnia, described as sudden onset of sleep. He was frequently found asleep in the shower. One episode lasted 48 hours, from which he could not be aroused despite rigorous verbal and tactile stimulation. Myoclonus worsened during hypersomnia. Although still functioning well at home, he began noticing vague difficulties concentrating at work. Detailed neuropsychological testing showed mild impairment of memory and executive skills. His neurological exam now revealed segmental myorhythmia of bilateral arms and abdominal muscles, limited upward saccades, blunted vertical optokinetic nystagmus, dysarthria, dysmetria, and ataxia (see Video 1). During his hospital admission, oculo-facial-skeletalmyorhythmia was seen during episodes of hypersomnia. He also reported a marked weight loss over the previous 3 months, along with a 10-year history of occasional arthralgia and low-grade fever, strengthening the clinical suspicion of Whipple's disease.Polysomnography showed that sleep was associated with worsening of myorhythmia characterized by 1-Hz flexion movements at the shoulders and elbows. Non-rapid eye movement (REM) parasomnia behaviors including somniloquy were also recorded. Multiple sleep latency test showed daytime hypersomnolence. Testing for HLA DQb1*0602, a genetic marker for narcolepsy, was negative.Multiple duodenal biopsies were negative, but CNS Whipple's disease was subsequently confirmed with positive cerebrospinal fluid (CSF) T. whipplei polymerase chain reaction (PCR). The patient received a 2week course of ceftriaxone, followed by maintenance trimethoprim-...

Persistence of Facio‐Skeletal Myorhythmia During Sleep in anti‐IgLON5 Disease

“…Moreover, in our patient myorhythmia displayed an unusual occurrence persisting during both wakefulness and sleep, as opposed to the state‐dependent pattern described in most well‐known etiologies, that typically desist in sleep 1 . Persistence of movements during sleep was also reported in the early descriptions of WD, even though without documentation from a specific neurophysiological study 6,7 . Subsequently, a report evaluating wake–sleep occurrence of myorhythmia through 24 hours VPSG highlighted that the apparent sleep‐persisting myorhythmia in WD was due to the inability to maintain a continuous and stable sleep stage 8 .…”

“…1 Persistence of movements during sleep was also reported in the early descriptions of WD, even though without documentation from a specific neurophysiological study. 6,7 Subsequently, a report evaluating wake-sleep occurrence of myorhythmia through 24 hours VPSG highlighted that the apparent sleep-persisting myorhythmia in WD was due to the inability to maintain a continuous and stable sleep stage. 8 Here we clearly demonstrate the persistence of myorhythmia through NREM and REM sleep stages, even before the development of the progressive and severe sleep dysfunction that characterized anti-IgLON5 disease.…”

Systematic review of movement disorders and oculomotor abnormalities in Whipple's disease

“…Whipple's disease (WhD) is a rare but treatable infectious disease from Tropheryma whipplei (TW), with an estimated incidence of 0.4 to 1.0 per 1,000,000 a year . The brain follows the gastrointestinal tract as the second major site of involvement, with CNS involvement on postmortem found in up to 50% of cases, most frequently in a periventricular and periaqueductal distribution . The percentage of clinical CNS involvement varies considerably, ranging from 6% to 63%, with most estimates of 10%‐43%.…”