An 84-year old right-handed gentleman presented with slurred speech and reduced mobility. Antecedent history included two stone weight loss and general decline associated with iron deficiency anaemia. The patient was a lifelong smoker on rivaroxaban for atrial fibrillation but lived independently with his wife.
On examination he had broken pursuit and bilateral gaze evoked horizontal nystagmus. He had cerebellar dysarthria, bilateral dysmetria and dysdiadochokinesis. There was normal tone and power, areflexia and equivocal plantar reflexes. He had significant gait ataxia and was unable to mobilise as a result. There was no evidence of sensory deficit to suggest sensory ataxia.
Computed tomography (CT) of the head at presentation demonstrated bilateral low-density change in the middle cerebellar peduncles (Figure 1A), which corelated to areas of elevated T2 signal demonstrating restricted diffusion on Magnetic resonance Imaging (MRI). These foci did not demonstrate enhancement following gadolinium administration. Small foci of restricted diffusion where also demonstrated in the pons. The initial impression was of an inflammatory disorder, or a possible para-neoplastic disorder, and standard stroke treatment was instigated given the foci of pontine restricted diffusion. Serology revealed an elevated Erythrocyte Sedimentation Rate (ESR) in keeping with an inflammatory process.
Lumbar puncture was performed and cerebrospinal fluid (CSF) examination showed a slightly elevated total protein but no oligoclonal bands (Table 1).
Following hospital admission general neurological deterioration was observed with progressive dysarthria, dysmetria and progressive cerebellar ataxia. A CT angiogram was performed and this demonstrated marked thickening of the common carotid arteries and branches extending to the skull base (Figure 2). In addition, the vertebral arteries also demonstrated significant wall thickening and occlusive narrowing on the right side in the V3 segment. The intracranial portion (V4) was significant narrowed and possibly occluded, however patency of the anterior inferior cerebellar arteries was confirmed on MR angiography (Figure 2), an important feature as the anterior inferior cerebellar arteries supply the middle cerebellar peduncles. As such the bilateral middle cerebellar changes was not felt to be purely ‘ischaemic’ in origin but represented an inflammatory process. At this point the patient received 1g of intravenous methylprednisolone and after 5 days this was converted to 60mg oral prednisolone to treat a large vessel vasculitis.
F18-Flurodeoxyglucose Positron Emission Tomography (PET-CT) demonstrated no evidence of FDG avid malignancy, however there was significant increased vascular uptake in the subclavian and proximal femoral arteries bilaterally suggestive of large vessel vasculitis. The patient had already been commenced on oral corticosteroids several days prior to PET-CT which may have reduced the degree of aortic or carotid artery uptake.
Serum immunoglobulin IgG and IgA were elevated and in particular IgG immunoglobulin was extremely high. It was of note that previous investigations by the general practitioner in the preceding weeks to admission had also demonstrated markedly elevated serum immunoglobulin as part of investigation of chronic weight loss. Immunoglobulin sub-class analysis confirmed elevated IgG4. The patient had further cerebellar symptoms and MRI at day 39 from admission demonstrated new foci of restricted diffusion in the cerebellar parenchyma, presumed to be ischaemic (Figure 3), the middle cerebellar changes persisted with regression of restricted diffusion and peripheral T2 shine-through, suggesting established post-inflammatory change. As screening for infection diseases was satisfactory mycophenolate mofetil 500mg twice daily was commenced. At day 60 surveillance imaging demonstrated a similar appearance to the middle cerebellar peduncles and established cerebellar infarcts (Figure 3).
Although pathological diagnosis for IgG4-RD is the gold-standard the current corona virus (COVID-19) pandemic restrictions, meant that the diagnosis was made without any tissue examination. We felt that the overall picture was compatible with IgG4-RD and the presence of high IgG4 in the serum was in keeping with the proposed diagnosis. Over the course of two months in-patient rehabilitation was slow but progressive with return to aided walking and improvement in gait and balance.