A 60-year-old Chinese woman, who was used to be a farmer, was admitted to our medical center due to recurrent vomiting and decreased level of consciousness for the past three years and the symptoms recurred during the recent 12 days. 3 years before administration, the patient developed nausea and vomiting coupled with decreased level of consciousness, elevated blood pressure, urinary incontinence, somnolence and mutism. During the episode of symptoms, blood pressure elevated to 150~170/80~100mmHg from baseline of 125/75mmHg. There were not any prodromal symptoms of fever, dizziness or headache before disease episode. Symptoms appeared periodically for every half a month or 2 months and lasted for about 7~10 days and could be relieved after usual supportive treatment. She became slow in response speed from 2 years ago.12 days before administration, the patient had similar symptoms with longer time. She had a past medical history of diabetes mellitus, cataract and family history of fundus macular hole.
The patient has a poor health condition with a body weight index of 17.6 kg/m2. Physical examination revealed blood pressure of 130/84 mmHg and body temperature of 36.1 °C. The neurological examination revealed that she was dysphoric and did not respond to external stimulation. Her right pupil was irregular after cataract surgery and left pupil was normal. Fine nystagmus was noticed in her right eye. Deep reflexes, including biceps reflex, triceps reflex, patellar reflex and Achilles reflex disappeared. Active movement of limbs were visible and muscular tone was decreased. Both Babinski sign and Chaddock sign were positive bilaterally.
Cranial computed tomography (CT) scan performed 3 years ago immediately after her first clinical episode showed diffuse low density in the bilateral paraventricular white matter. Further examinations were proposed to clarify the diagnosis after her administration. Laboratory examinations revealed elevated blood glucose of 7.17 mmol/L, decreased albumin of 35.8 g/L and a HbA1c concentration of 7.3%. Lumbar puncture was performed and the opening pressure was 140 cmH2O. Cerebrospinal fluid examination revealed no pleocytosis or elevated protein level and normal glucose level. Complete blood count, liver and renal functions, antinuclear antibody spectrum, ANCA series were normal. Viral markers, syphilis test, catecholamines, hematuria organic acid were negative. Enhanced adrenal CT scan did not find hyperplasia or adenoma. Brain magnetic resonance imaging (MRI) revealed mild cerebral atrophy and moderate cerebellar atrophy, and showed high intensity in the cerebral white matter on T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR) and in corticomedullary junction on diffusion-weighted imaging. The video electroencephalogram (EEG) showed asymmetrical posterior rhythm with lower amplitude on the left side. Nerve conduction studies showed a multiple and symmetrical reduction in both motor and sensory nerve conduction velocity. Screening of thoracic CT scan, abdominal and gynecological ultrasound did not find sign of tumor. Skin biopsy performed in left leg showed chronic inflammatory cells infiltration in hematoxylin and eosin staining and intranuclear inclusions in adipocytes, sweat gland cells and fibroblasts in immunohistochemical staining and under electron microscope.
Three days after nutrition support therapy, the patient regained consciousness and was able to communicate in language, while the memory and understanding was impaired. Her mini mental state examination (MMSE) score and frontal assessment battery (FAB) score were 12/30 (illiterate) and 4 (14.5/18), respectively. Mild weakness was present in both upper and lower limbs. Algesthesia, pallesthesia, topognosis were abated in the right side. Coordinate movements were steady and accurate. Orthostatic hypotension was observed in Schellong test, with a decrement of systolic blood pressure by 22mmH2O. The fragile X mental retardation1 (FMR1) permutation repeats of CGG was in normal range. With all the data from clinical examination listed above, we diagnosed her with adult-onset neuronal intranuclear inclusion disease(NIID).