Unsteady gait

The patient is a 42-year old African American female who presented to an outside hospital with a chief complaint of increasingly unsteady gait and dizziness over a 4 month period. A brain MRI on admission did not reveal a clear etiology. The past medical history is significant for a 2 year history of eating mothballs and toilet-bowl fresheners. As the history was deemed inconsistent with naphthalene toxicity the patient was transferred to Psychiatry for treatment of suspected conversion disorder. Past medical history is also significant for a remote history of major depression with psychotic features, and status post gastric bypass. Medications at the time of admission consisted of Wellbutrin SR 150 mg QD and Cogentin 1 mg BID.

Over three weeks her neurologic status deteriorated, with speech becoming slow and hypophonic. Complete mutism ensued. The patient went on to develop cogwheel rigidity, and became unable to walk. The patient was transferred to The Johns Hopkins Hospital. EEG showed slow activity over the left occiput. Brain SPECT imaging was normal. TSH, RPR, Lyme testing, urine toxicology, 24-hour urine for heavy metals, serum anti-Purkinje cell antibodies and CSF 14-3-3 protein were all normal. Three lumbar punctures showed normal CSF glucose and white blood cells with negative bacterial and viral cultures. Therapeutic trials of antidepressants, antipsychotics and benzodiazepines for presumed primary psychiatric catatonia produced no clinical improvement.

Major depression with psychotic features
Gastric bypass (1998)
Psoriasis

The patient's family history is unremarkable.

Primary family contact is her brother.

Folic acid 1 mg PO QD
Thiamine 100 mg PO QD
Multivitamin 1 PO QD
Ferrous sulfate 325 mg PO TID
Lovenox 40 mg QD
Vitamin B12 1000 mcg IM every month

No known drug allergies.

Weight: 60.1 kg T: 37.6 C BP: 136/80 P: 78 R: 20
General: African American female; alert but non-interactive
Neuro: Moving all four extremities to pain with increased tone and cogwheeling; 2+ reflexes throughout with down-going toes
HEENT: Positive doll's eyes, positive corneals, no facial droop
CV: Sinus tachycardia
Lungs: Clear to auscultation bilaterally. No wheezes, rales or rhonchi.
Abdomen: Soft and non-tender
Extremities: No cyanosis, clubbing, or edema.

Na 142; K 3.8 ; Cl 106 ; BUN 8 ; Glucose 104; Cr 0.4; Ca 9.0; Phos 3.8 ; Mg 1.3
Tot protein 5.8; Albumin 3.3; Vit B12 303 ; TSH 1.8
TBili 0.1; ALT 137; AST 28; Alk Phos 103; CO2 22;
WBC 11,530 ; Hct 30.0; Plt 509,000
Urinalysis: large leukocyte esterase and positive nitrite
Bacterial culture, urine: greater than 100,000 colonies of E. coli and E. faecalis

Figure 1. (6/4/04) Fluid-attenuated inversion recovery (FLAIR) images show nearly symmetric, mildly elevated signal in the periventricular cerebral and deep cerebellar white matter without associated mass effect. Mild global volume loss for age is noted.

Figure 2. (6/4/04) Proton MR spectroscopic imaging (TR/TE= 1700/280 ms) show elevated Choline and reduced NAA in the T2/FLAIR hyperintense white matter bilaterally in the frontal and parietal lobes. Spectra are consistent with demyelination and axonal loss or dysfunction secondary to toxic encephalopathy.

The patient was mute, severely bradykinetic with moderate rigidity, and dystonic hand posturing but able to follow simple commands such as "wiggle your toes" when she arrived and was admitted to the Neurology service. Multiple EEGs showed diffuse slowing. MRI revealed diffuse abnormality of the cerebellar hemispheres along with periventricular and splenial hyperintensity. MR spectroscopy showed demyelination and axonal loss. EMG showed acute denervation in the lumbosacral, thoracic, and cervical myotomes. Urine porphyrins, serum ceruloplasmin, and thiamine levels were normal. Radiologic search for an occult malignancy was negative. A urinary organic acid assay to assess for possible mitochondrial disease showed the presence of 2,5- dichlorophenol (DCP), a paradichlorobenzene metabolite (a common household deodorant and pesticide founding room deodorizers, toilet bowl fresheners, and some mothballs) more than 2 months after initial hospitalization. Napthalene was not detected.

During the hospital stay she remained nonverbal and minimally responsive. She attended to examiners with her eyes, intermittently showed two fingers to command, sporadically waved goodbye to the team exiting the room, and attempted to verbalize on several occasions. Therapeutic trials of methylphenidate and carbidopa-levodopa produced no improvement. A gastrostomy tube was placed and she was discharged to a rehabilitation facility.

What is the most likely cause of the patient's neurologic dysfunction?