Hypometabolism in cerebellar tonsil and flocculus regions during downbeat nystagmus

A 66-year-old female patient presented with a 2-year history of a downbeat nystagmus syndrome (DBN) of unknown etiology with distressing oscillopsia that increased on lateral gaze or after quick head movements, and consecutive postural instability with repeated backward falls. She was examined twice by 3-D video-oculography (VOG) and 18F-fluorodeoxyglucose (FDG)-PET on and off treatment with 4-aminopyridine (4-AMP), a potassium channel blocker known to significantly improve DBN [1].

Careful neurological, neuro-physiological (electro-oculography with caloric testing, blink- and masseter reflexes), and neuro-orthoptic examinations (including subjective visual vertical) were performed to exclude additional central nervous system disorders. Eye movements were recorded by means of monocular 3D-VOG using black scleral markers and an infrared camera; data were analyzed off-line [for details 2]. The patient underwent two PET scans following injection of 170 MBq FDG in an ECAT Exact PET Scanner (Siemens/CTI, Knoxville) under standard conditions [3] with eyes closed: A) first without medication and B) 4 months later during 4-AMP treatment. Standardized three-dimensional stereotactic surface projections of the individual dataset as well as parametric z-score images were generated in order to compare the patient data with a normal database using NEUROSTAT and SPM99 software.

4-AMP reduced mean slow phase velocity of the DBN significantly from 50°/s to 3°/s in VOG. Both FDG-PETs, on and off 4-AMP, showed a reduced cerebral glucose metabolism in the region of the cerebellar tonsil and flocculus/paraflocculus bilaterally in the individual dataset and compared to the normal database. Analysis of the region of interest revealed that this hypometabolism tended to be reduced during 4-AMP. No signal change in the brainstem or other cerebellar structures was found.

Cerebellar structures like the tonsil and (para-)flocculus seem to play a crucial role in DBN by physiologically inhibiting projections to the vestibular nuclei that mediate upward eye movements. The hypometabolism in these cerebellar structures in our patient might reflect a disinihibition of vestibular circuits, thus causing DBN. The PET scan with 4-AMP appeared to reveal a milder glucose hypometabolism, which probably represents an improvement of the cerebellar inhibition.

1) Strupp et al. Neurology 2004

2) Schneider et al. J Neurophysiol 2002

3) Bartenstein et al. Eur J Nucl Med 2002