42‐Year‐Old Man with Worsening Headache

Clinical History

A 42‐year‐old man with a history of asthma, sinusitis and GERD presented to the critical care unit with a six‐day history of worsening headache, nausea and vomiting. He reported that the symptoms began with a “popping” sensation after a bout of coughing and fever, although he was afebrile on admission. Neurological exam revealed that he was sleepy, but easily arousable and oriented × 3 with a non‐focal motor exam. CT scan showed a large right temporal‐occipital hyperdense lesion with surrounding edema suggestive of an acute/subacute hemorrhage and a 4–5 mm of associated midline shift with no evidence of hydrocephalus. On day 2, he developed a 4/5 left‐sided hemiparesis, dysarthria and a left hemifacial weakness. MRI of the brain demonstrated a large right temporal‐occipital intraparenchymal hemorrhage, subtle leptomeningeal enhancement, an increased T2 signal of the brainstem especially within the right pons and a partial thrombosis of the right transverse and sigmoid sinuses (Figure 1A,B). There was no evidence of the underlying tumor or vascular malformations. He developed a worsening of the left hemiparesis (2/5) and was started on heparin anticoagulation for a suspected venous infarct, secondary to the venous sinus thrombosis. On hospital day 4, he was noted to be more alert with improvement in his speech. Repeat MRI showed recanalization of the transverse sinus and stable abnormalities in the brainstem and right temporal‐occipital lobes. He remained awake, alert and oriented with some improvement in his hemiparesis. On day 8, he had a sudden neurological decline, became hemodynamically unresponsive and ultimately expired despite aggressive medical management.

Figure 1.

Postmortem Neuropathology

There was moderate cerebral edema, with uncal and bilateral cerebellar tonsillar herniation, worse on the right. There was a right‐sided hemorrhagic lesion which extended from the level of the posterior hippocampus to the tip of the occipital lobe. The lesion consisted of multiple partially connected areas of recent hemorrhage within what appeared to be necrotic tissue measuring approximately 5.0 × 4.0 cm in greatest area. The lesions were predominantly within the white matter, although involvement of the gray matter was also noted. A similar hemorrhagic lesion was seen in the pontine base with extension to the tegmentum bilaterally, more prominent on the right and measuring 2.8 × 2.0 cm, involving the entire thickness of the pons (Figure 1C). There were extensive areas of coalescence of hemorrhagic lesions. The remainder of the uninvolved cerebral cortical ribbon, cerebral white matter and basal ganglia were unremarkable. Microscopically, the lesions were predominantly within the white matter, although gray matter extensions were also noted. There were multiple hemorrhages, often with a typical perivenular, ring and ball pattern (Figure 1D). Multiple blood vessels, predominantly venules, displayed fibrinoid necrosis accompanied by neutrophilic infiltrates and necrosis of adjacent tissue (Figure 1E). Myelin stains defined the necrotic and hemorrhagic lesions within the white matter with relative preservation of tissue adjacent to the lesions (Figure 1F). Additionally, there was no evidence of hypoxic injury seen in uninvolved areas of the brain. Bielschowsky defined the areas of white matter destruction and highlighted large numbers of axonal bulbs and spheroids, as well as neuritic fragments (Figure 1G). What is your diagnosis?

Final Diagnosis

Acute Hemorrhagic Leukoencephalitis (AHL) – Weston‐Hurst's disease

Discussion

The clinical and neuropathologic features are typical of AHL or Hurst's disease.

Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune‐mediated inflammatory demyelinating disease which can progress to a fulminant, fatal and rare disorder known as AHL or Hurst's disease 2, 4. The clinical, radiographic and neuropathologic features seen in this case are typical of the latter. Though the exact etiologies are unknown, both ADEM and AHL are thought to be preceded by an immunologic trigger, in the form of a viral upper respiratory tract infection 1–4 weeks before clinical symptoms manifest 1. ADEM occurs predominantly in the pediatric age group, and is thought to be due to immature myelin, though it can present at any age. Neurologic symptoms develop subacutely and evolve to hospitalization within days. Symptoms common to both adult and pediatric cases include ataxia, altered consciousness, signs of encephalopathy, decline in neurological function and brainstem symptoms. However, adults present more frequently with motor and sensory deficits compared to pediatric patients, which present with fever and headaches. Characteristic neuroimaging findings of ADEM include hyperintense multifocal, diffuse, white matter lesions with indistinct margins on T2/FLAIR. Gray matter lesions most commonly include bilateral thalamus and basal ganglia involvement. Mass effect and edema are seen with larger lesions 3. Histological features include perivascular axon‐sparing demyelination and infiltration of vessel walls by lymphocytes, plasma cells and monocytes. In AHL, characteristic lesions are perivascular hemorrhagic demyelinating lesions with edema, axonal injury, meningeal inflammation and neutrophilic infiltrates 1. Hemorrhagic lesions are most concentrated in the white matter and the pons. Clinical symptoms are similar to ADEM except neurological deterioration occurs within hours. Earlier literature usually describes the disorder as fatal, but currently better outcomes have been reported. No specific treatment is available and clinical management is supportive in nature. Survival is rare in AHL, except in a small number of pediatric cases where early treatment with craniotomy, IVIG and corticosteroids was implemented.