Hallervorden Spatz disease: MR imaging.J Shah, D Patkar, T Patankar, A Krishnan, S Prasad, J Limdi
Department of Radiology, Dr. Balabhai Nanavati Hospital, Mumbai, India., India
Three patients were diagnosed as suffering from Hallervorden Spatz disease, a rare disorder, on the basis of their clinical and MRI findings.
Keywords: Adult, Case Report, Child, Female, Globus Pallidus, pathology,Hallervorden-Spatz Syndrome, diagnosis,Human, Magnetic Resonance Imaging, Male,
Hallervorden Spatz disease (HSD) is a rare familial recessive disorder, though occasionally, non-familial sporadic cases have been reported,,. Clinical presentation is characterized by relentless progression of the extra-pyramidal dysfunction and intellectual decline at a young age. Pyramidal signs and retinal degeneration are frequently associated,,. Characteristic pathological findings in HSD are neuroaxonal swelling and iron deposition in the globus pallidi of the lentiform nuclei,,. Magnetic resonance imaging (MRI) can detect these features,. We describe three cases in which clinical picture and MR findings suggested the diagnosis of HSD.
A seven-year-old male child presented with mental retardation, motor difficulties and speech problems. Symptoms started four years ago with unsteady gait and progressed to generalized motor difficulties with dysarthric speech. His paternal uncle had died 14 years ago at the age of 13, after suffering from mental retardation and motor disabilities. The exact diagnosis and investigative findings were not available. No other living family member had any similar complaints. Neurological examination revealed impaired higher functions and marked diffuse rigidity (both extra-pyramidal and pyramidal, more marked in the lower limbs). Tone was increased. Deep tendon reflexes were brisk. Babinski's sign was positive. Speech was incomprehensible. Minimal retinal degeneration was present in the temporal regions. Serum copper and ceruloplasmin levels were normal. MRI [Figure - 1], [Figure - 2] revealed hyperintense areas in both the globus pallidi, surrounded by a hypointense rim, giving a target like appearance to the globus pallidi on T2WI. Mild cerebellar atrophy was also present. Substantia nigra and other portions of the basal ganglia did not reveal any abnormality.
A 23-year-old man was relatively asymptomatic till the age of 12 years, when he started developing tremors and gait impairment. These abnormalities progressed over the years with slowing of voluntary movements, rigidity of limbs and dystonic posturing. Speech was slurred. Mild impairment of higher functions was also seen. No significant family history was obtained. Neurological examination revealed slurred speech, diffuse rigidity, brisk deep tendon reflexes and positive Babinski's sign. Laboratory, investigations, including serum copper and ceruloplasmin levels were normal. CT scan done three years prior revealed hypodensities in both the globus pallidi. MR scan [Figure - 3], [Figure - 4] revealed hyper-intensity in both the globus pallidi, surrounded by hypointense rim peripherally on the T2WI. The hypointense rim was more marked along the lateral aspect of the globus pallidus. Pars reticulata of the substantia nigra did not reveal any exaggerated hypointensity.
A 11-year-old girl presented with progressively increasing mental retardation and extra-pyramidal symptoms, since the age of four years. Speech was also grossly abnormal. She was completely bed ridden for the past six months. No significant family history was obtained. Physical examination revealed flexor contractures of the four limbs with increased tone and brisk tendon reflexes. Ophthalmic examination was within normal limits. Laboratory investigations were unremarkable. Serum copper and ceruloplasmin levels were normal. MR scan [Figure - 5] revealed both hypointense (posterolaterally) and hyperintense (antero-medially) changes in the globus pallidi, which were bilaterally symmetrical. Few areas of demyelination were also noted in the frontal lobes.
HSD is an uncommon metabolic disorder, first described in 1922. Both hereditary (autosomal recessive transmission) and sporadic cases have been described,,. The age of onset is usually in late adolescence. However, younger and older cases have been reported,,. It is characterized by relentless progression of the extra-pyramidal symptoms (gait impairment rigidity of the limbs, slowing of the voluntary movements, choreo-athetosis. dystonic. Posturing, spasticity, tremors, dysarthria) mental deterioration (dementia), optic nerve atrophy, or retinal degeneration and pyramidal signs. Other familial causes of extra-pyramidal-dementia complex are Wilson's disease, Huntington's chorea, olivo- ponto-cerebellar atrophy, and Joseph's syndrome,,,.
On gross evaluation of the autopsied brain, generalized atrophy is associated with decreased size of the caudate nucleus, substantia nigra and tegmentum. Histopathology reveals neuronal loss, axonal swelling (called as "Axonschollen", "Neurono- axonal systrophy" or "Axonal Spheroids" - i.e. axonal cells showing vacuolated cytoplasm) gliosis and iron deposits (mainly, in globus pallidi. substantia nigra, caudate nucleus, amygdala, hippocampus and pons),,,. Radionuclide imaging with 59Fe shows delayed uptake and disappearance in the globus pallidi. However it is not found to be consistent enough to be of clinical utility. No biological markers have been found in HSD. The diagnosis is based on clinical and pathological findings. Imaging can play a major role in antemortem detection of the pathological changes,,,.
Perry et al have found deficiency of cysteine dioxygenase and subsequent cysteine accumulation in the globus pallidi, in HSD. They have proposed that accumulated cysteine chelates iron, leading to its deposition. Free radicals of iron and cysteine damage neuronal cell membranes. There occurs swelling of the terminal portions of the axons due to accumulation of the damaged cellular constituents and products. These "Spheroids" expand the myelin sheaths and cause its disintegration. This demyelination is accompanied by reactive gliosis.
CT scan usually shows hypodensity in both basal ganglionic regions, along with mild to moderate atrophy of the brain and basal ganglionic regions, due to gliosis. However, high-density calcifications in the globus pallidi without any atrophy have also been described.
MR offers the possibility of detecting iron deposition in the brain. On T2WI (long TE/TR), iron causes local non-homogeneity in the magnetic field, which dephases spin and produces loss of signal. So, iron deposition areas are seen as hypointense areas. Other pathological features like gliosis, demyelination, neuronal loss, axonal swelling etc. are seen as high signal intensity areas on T2WI. So, both hypo and hyperintense lesions are seen on imaging. These changes are mostly seen in the globus pallidi and are bilaterally symmetrical,,,,. Initially, hyperintense areas are seen the globus pallidi and substantia nigra. Later, as the disease progresses, a hypointense rim is seen around it, due to iron deposition. Evolution of the findings suggests that neuro-axonal degeneration is followed by pallido-nigral pigmentation. Pallido-nigral iron deposition is only a late phenomenon,. Sethi et al have described these changes as the "eye-of-the- tiger" sign. This sign was also seen in all our three cases. Two groups of HSD have been described. In group I, both globus pallidi and pars reticulata of the substantia nigra are involved and show iron deposition. Whereas in-group III, only globus pallidi are involved,. Iron deposition causing low signal intensity can be better seen on higher strength magnet. Occasionally, calcium deposition can also occur, as seen on CT. It also produces low signal. They are usually very tiny and are limited to much smaller area than the deposits of iron, which involve the whole globus pallidi, upto it's edges, as demonstrated by magnetic susceptibility effects observed on MR.
High signal areas on T2WI in the globus pallidi can be seen in variety of lesions including ischaemia, few metabolic disorders and organic acidurias. Other disorders affecting the basal ganglia e.g. Wilson's disease, Leigh's disease. mitochondrial encephalopathies and infantile bilateral striatal necrosis - more frequently involve the neostriatum, particularly the putamen rather than the globus pallidus of the lentiform nucleus.
Deposition of iron and other physiological segments in the globus pallidi and substantial nigra (hypointense on T2WI) have. also been reported in encephalitis, Wilson's disease. idiopathic haemochromatosis, myoclonic epilepsy, radiation exposure, storage disorders and even normal aged brain,, which can be differentiated based on clinical history and examination.
In conclusion, when a young patient presents with relentlessly progressive extra-pyramidal symptoms and mental deterioration with typical MR appearances of bilaterally symmetrical hyperintense changes (gliosis) with peripheral hypointensity (iron deposition) in the globus pallidi on T2WI a possibility of HSD needs to be strongly considered. Clinico-imaging features are fairly diagnostic of HSD even in the absence of the histopathological confirmation of the disease in the globus pallidi.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]