A 63-year-old woman was admitted to our hospital with a 7-day history of asthenia, postural instability and falls. Her past medical history included hypertension, Hashimoto's thyroiditis (with detectable anti-thyroglobulin and anti-peroxidase autoantibodies), benign leukopenia and cervical arthrosis. She worked as a yoga teacher before admission. The patient had no history of vaccination or viral infection in the last year. Fifteen days before the onset of the symptoms she had started a homeopathic treatment for cervical pain. The formulation of tablets (labelled as ‘immunostimulant’) consisted of Echinacea purpurea 45 mg, Uncaria tomentosa 37.5 mg, and Tabebuia avellanedae and Plantago maritima 30 mg.
On admission, vital signs were normal. The patient was awake, alert and oriented. Neurological examination revealed the presence of left-eye horizontal nystagmus, mild dysarthria, and mild right arm weakness together with both axial and appendicular ataxia. The rest of the physical examination was unremarkable. Blood test showed mild leukopenia (without neutropenia) as the only altered parameter.
Cranial T2-weighted and FLAIR sequences on magnetic resonance image (MRI) showed pseudonodular, subcortical and periventricular bilateral white matter lesions with heterogeneous gadolinium enhancement. High signal on an apparent diffusion coefficient map was compatible with vasogenic edema (fig. ). Cerebrospinal fluid (CSF) analysis showed a mild increase in protein concentration (60 mg/dl, =45 mg/dl) without pleocytosis. CSF cultures were negative. CSF and serum oligoclonal bands, CSF VDRL and herpes simplex virus PCR were negative. Antinuclear antibodies were undetectable.
Fig. 1 a MRI showed pseudonodular, subcortical and periventricular bilateral white matter lesions with heterogeneous gadolinium enhancement. b Repeat MRI on hospital day 6, showing progression of the previously described lesions and involvement of the cerebellum. (more ...)
On hospital day 6, central right facial nerve paralysis was observed. On the following day, the patient became lethargic and bilateral clonus and Babinski signs were present. The patient was admitted to the intensive care unit (ICU) because of impaired consciousness, and intravenous methylprednisolone was started, due to the presumptive diagnosis of a central nervous system (CNS) demyelinating process. The patient developed generalized tonic clonic seizures requiring anti-convulsant therapy, sedation and mechanical ventilation. Repeat MRI showed progression of the previously described lesions and involvement of the cerebellum (fig. ).
Computer tomography (CT)-guided stereotactic biopsy was performed, and pathology demonstrated features compatible with acute demyelination (fig. ). Brain biopsy PCR was negative for Mycobacterium tuberculosis, JC and BK viruses. The biopsy specimen was reviewed for the presence of an immune cell infiltrate using immunohistochemical markers for T cells (CD3) and B cells (CD20). The tissue harbored a considerable immune cell infiltrate including significant numbers of T cells that were distributed throughout the tissue (fig. ) and present in more compact clusters (fig. ). B cells were fewer in number than T cells and more sparsely distributed (fig. ) although they were also present in more compact clusters (fig. ).
Immunohistochemistry. a, b CD3 markers for T cells. c, d CD20 markers for B cells. See text for further details.
Total treatment scheme included 3 g methylprednisolone i.v., oral steroids, five plasma exchange sessions and 120 g immunoglobulin i.v., without major improvement of the symptoms that required treatment in our ICU. After 2 months of respiratory assistance, the patient was released from mechanical ventilation. However, no significant neurologic recovery was achieved.
The patient was discharged to a rehabilitation facility; she was quadriparetic, required help in daily activities, and was fed through a percutaneous endoscopic gastrostomy tube. Her level of consciousness was impaired and she was barely able to connect with her family members. A follow-up brain MRI at 8 months showed atrophy and scarring; no new lesions had occurred (fig. ). Two years after the initial demyelinating event, the patient died of septic shock.