Hereditary diffuse leucoencephalopathy with spheroids (HDLS) is a rare inherited progressive leucoencephalopathy characterised by giant neuroaxonal swellings (spheroids) within the CNS white matter.The case is reported of a 45 year old woman with a rapidly progressive fulminant illness course characterised by progressive cognitive decline with depressive features. A presumed dominant inheritance pattern was elicited. This report reviews the literature on HDLS and the relation of this disorder to other conditions with giant neuroaxonal swellings.A 45 year old white woman presented with a 16 month history of progressive cognitive decline characterised by depressive symptoms: emotional blunting, lack of spontaneity, lack of initiation, and disturbed diurnal rhythm. The patient had developed the problem of wandering through the house at all hours and required assistance from her family for activities of daily living. An initial psychiatric consultation four months before neurological review suggested a depressive illness; however there was little improvement with the use of a serotonin re-uptake inhibitor for four months. The patient was admitted for neurological assessment because of poor memory, declining cognitive function, insomnolence, distractibility, prominent nocturnal wandering, and urinary and faecal incontinence, which was thought unrelated to a depressive illness. She had not undergone any neurosurgical procedures or received any human derived pituitary hormone therapy. She had travelled to the United Kingdom in the preceding five years.Physical examination revealed a middle aged woman with no dysmorphic features. Affect was bland with a Folstein MiniMental State examination of 24 of 30, with particular areas of deficit in recall and calculation. Pronounced verbal perseveration was noted. There was no excessive startle response. The gait was broad based and the left arm was held in a flexed posture and was not used in normal activities. A pronounced grasp response was noted in the left hand but no other frontal release signs were noted. Cog wheeling rigidity of the left arm was noted and the left arm would drift downwards. Reflexes were increased on the left with an extensor plantar response on the left. Mild incoordination was noted with left greater than right. Power was preserved throughout. Sensory examination to all modalities was normal. The patient had no clinical evidence for a peripheral neuropathy. There were no skin changes, bony deformities, hepatosplenomegaly, or Kaiser Fleischer rings seen. The patient's hair was straight.Laboratory investigations were normal and included the following: electrolytes, full blood count, liver function tests, ammonia, thyroid function tests, copper, vitamin B12, folate, syphilis and HIV serology, vitamin E, lactate, amino acids, arylsulfatase A and galactocerebrosidase in leucocytes, sialic acid, very long chain fatty acids, antinuclear antibody, antineuronal nuclear antibodies, angiotensin converting enzyme, antineutrophil cytoplasmic antibodies, erythrocyte ...
