RESIDENT & FELLOW SECTION Clinical Reasoning: Section Editor A 27-year-old man with acute-onset ataxia John J. Millichap, MD Jorge Risco, MD SECTION 1 Examination revealed saccadic visual pursuit Menachem Weiss, BS A 27-year-old man with a history of diabetes mellitus with intact voluntary saccades. There were no square (DM) and asthma presented to the emergency depart- wave jerks or nystagmus. Speech was dysarthric. ment 1 month after the onset of dysarthria and ataxia. Cranial nerve examination was otherwise normal. Correspondence to The symptoms were noted abruptly upon waking. He Strength was preserved, but the patient’stonewas Dr. Risco: swayed on standing, fell easily, and noted tremor [email protected]. diffusely diminished. Vibratory sensation was 2 sec- edu when manipulating objects. His speech was nearly onds at the toes with otherwise preserved sensation. unintelligible. He also had 1 month of mild distal par- Deep tendon reflexes were absent in upper and esthesias and a 30-pound unintentional weight loss. lower extremities. Plantar responses were flexor He denied diplopia, dysphagia, preceding illness, or bilaterally. The patient had marked ataxia on other systemic symptoms. Over the course of the finger-to-nose and heel-to-shin with intention month, his dysarthria improved but his imbalance re- tremor, dysrhythmokinesia on hand tapping, and mained unchanged. His delay in seeking medical dysdiadochokinesia with rapid alternating move- attention was due to lack of health insurance. ments. Stance was stable with no truncal ataxia. The patient’s type 2 DM was diagnosed in adoles- Romberg was positive with subtle sway with eye cence. It was initially controlled with metformin and closure. Gait was wide based; he was unable to tan- then insulin. As an adult, he lost health insurance cov- dem walk. erage. He subsequently self-medicated with sporadic Questions for consideration: doses of insulin. He had a 3-pack-year tobacco smoking history, consumed 3 ounces of alcohol per week, and 1. Where does this process localize? used marijuana once per week. He worked in construc- 2. What is the differential diagnosis for acute-onset tion, fireproofing, and insulating old buildings. ataxia? GO TO SECTION 2 From the Department of Neurology (J.R.), University of Rochester Medical Center; and University of Rochester School of Medicine (M.W.), NY. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2017 American Academy of Neurology e207 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. SECTION 2 manganese). Our patient worked in old buildings, The patient’s examination revealed cerebellar dys- which can be a source of mercury intoxication. Post- function and peripheral polyneuropathy. Severe infectious viral cerebellitis typically occurs in chil- proprioceptive deficits can result in a sensory appen- dren, yet has also been described in young adults dicular ataxia. In this patient, the degree of sensory secondary to Epstein-Barr virus. impairment did not account for the severity of the Since our patient also had a peripheral neuropa- appendicular ataxia. Cerebellar dysfunction was thy, diagnoses unifying it and the cerebellar ataxia supported by the presence of dysdiadochokinesia, should be considered. His history of unintentional dysrhythmokinesia, intention tremor, saccadic pur- weight loss raises concern for malignancy and an suits, and dysarthria. associated paraneoplastic syndrome. Classically, The differential diagnosis for cerebellar ataxia can anti-Hu manifests with cerebellar degeneration be narrowed by the timing of clinical onset. Causes of and neuropathy. Vitamin deficiencies can also cause acute-onset ataxia include 3 categories of pathology: both cerebellar and peripheral nerve involvement vascular, toxic, and infectious. Both ischemic and (B1,B12, E). In contrast to our case, these disorders hemorrhagic posterior circulation strokes should be present subacutely. considered. Acute-onset ataxia can also result from Questions for consideration: exposure to medications (antiepileptics, antineoplas- tics, lithium salts, metronidazole), recreational drugs 1. What investigations would you order? (alcohol, phencyclidine), and environmental toxins 2. Can the peripheral neuropathy and cerebellar (carbon tetrachloride, bromides, toluene, mercury, ataxia be accounted for by a unifying diagnosis? GO TO SECTION 3 e208 Neurology 88 May 30, 2017 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Figure Axial head MRI (A) Axial T2 brain MRI shows symmetric hyperintensity of the pons with relative sparing of the corticospinal tracts and hyperintensity of the paramedian cerebellar folia; (B) T1 contrast enhancement within a similar pontine distribution; and (C) a diffusion-weighted image shows restricted diffusion within a sim- ilar cerebellar distribution. SECTION 3 EMG revealed a moderate, length-dependent The patient was admitted to the hospital for an expe- motor and sensory, predominantly axonal, polyneur- dited workup. MRI of the brain showed symmetric opathy. This was compatible with a diabetic neuropa- signal abnormalities in the pons and cerebellum (fig- thy, in the context of uncontrolled hyperglycemia. ure). Laboratory testing identified uncontrolled There were no clinical features that conflicted with this DM. His blood glucose peaked at 708 mg/dL early possibility, such as asymmetry, rapidly progressive in his hospital course and his HbA1c was 15.9%. A coarse, motor greater than sensory deficits, or proximal lumbar puncture revealed elevated protein (207 mg/ greater than distal deficits. Other testing for the neu- dL) and elevated glucose (194 mg/dL) but no pleo- ropathy was unremarkable: antinuclear antibody, cytosis. The remainder of his workup was unremark- anti-Ro, anti-La, serum and urine protein electropho- able: complete blood count, basic metabolic panel, resis, HIV, and syphilis were normal or negative. vitamin B12, vitamin E, heavy metals (mercury and Questions for consideration: lead), CSF paraneoplastic panel, and CSF viral PCR for Epstein-Barr virus, herpesvirus, and varicella- 1. What is the diagnosis? zoster virus were normal or negative. 2. What is the prognosis? GO TO SECTION 4 Neurology 88 May 30, 2017 e209 ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. SECTION 4 can occur in the cerebellum, thalamus, basal ganglia, Our patient’s MRI revealed symmetric signal abnor- hippocampus, or mesencephalon. Injury of these struc- malities within the pons and cerebellum. The sym- tures can manifest with ataxia, behavioral changes, par- 3,6–8 metry suggests toxic, metabolic, and genetic kinsonism, dystonia, or chorea. Presentations range categories of pathology. Metronidazole and methyl in severity from mild symptoms to coma. Relevant to bromide intoxications can produce symmetric imag- our patient, the cerebellum is the most common ex- ing findings in the pons and cerebellum, among other trapontine structure affected in ODS. structures. Pontine involvement is limited dorsally MRI has become essential in establishing a diagno- and cerebellar involvement limited to deep nuclei. sis of ODS. The imaging hallmark is strikingly sym- These intoxications are unlikely in our patient, given metric signal abnormalities, accounted for by diffuse the lack of exposure and incompatible imaging. metabolic pathophysiology. Restricted diffusion is Genetic causes are also unlikely, given the clinical the earliest and most sensitive acute finding. T2 hy- course of acute-onset symptoms followed by perintensity is commonly seen, yet can be delayed improvement. Among metabolic disorders, osmotic for weeks after the symptom onset. Thus, follow-up demyelination syndrome (ODS) frequently affects imaging may be required in patients with normal ini- the pons and can also affect the cerebellum. In this tial imaging. Both T1 hypointensity and contrast 9 disorder, the pons characteristically has a trident- enhancement are seen in a minority of cases. shaped signal change due to relative sparing of the Our understanding of the prognosis in ODS has corticospinal tract. This pattern of injury was present evolved over time. When first recognized in autopsy in our patient (figure, A). cases, ODS was thought to be rare and invariably fatal. Our patient was diagnosed with ODS and periph- Advances in imaging have allowed the recognition of ’ eral neuropathy from uncontrolled DM. His delayed this disorder s spectrum. Half of affected patients presentation to the hospital posed a diagnostic chal- recover and regain independent function, one-quarter 4 lenge. It is unclear what his metabolic homeostasis remain disabled, and one-quarter die. Favorable out- was at the time of injury. Nevertheless, his diagnosis comes are predicted by higher Glasgow Coma Scale . was made in the context of characteristic imaging, the scores on presentation ( 10 points), less severe hypo- . risk of rapid fluctuations in osmolarity, and by nega- natremia ( 115 mEq/dL), and the absence of concom- 8 tive tests for alternate causes of acute-onset ataxia. itant hypokalemia. The extent of signal abnormalities 10 ODS is the degeneration of oligodendrocytes and on MRI does not predict clinical outcome. their myelin caused by a rapid rise in extracellular osmo- Our patient was started on insulin (glargine 15 – larity. Cells normally