Overview.
Pallidocytic nigrostriatal pigmentary degeneration is a hereditary disorder associated with impaired iron metabolism and primarily involves the extrapyramidal system. It is also known as Hallervorden-Spatz disease. It is an inherited metabolic disease of late childhood and adolescence. The disease is inherited in an autosomal recessive manner. Neurodegeneration with neuronal deafferentation and gliosis is caused by deposition of iron salts bilaterally in the pallidum, substantia nigra pars reticulata, or even to the red nucleus. It is often categorized into childhood and adult forms, with the childhood form being the most common, starting between 6 and 12 years of age. Adult type is also known as late-onset, usually at the age of about 55 years old, often with a family history of tonic hypermobility, static tremor, easy to fall, slow articulation, low voice, small steps, a few patients are afraid of the light, swallowing inconvenience, incontinence, mental retardation, or even dementia, pigmented retinitis, and may have optic disc atrophy disease duration of up to more than 10 years.
Etiology
The etiology of the disease is still not completely clear, and it is generally believed to be autosomal recessive, and Taylor found that the causative gene of the disease is located in the region of chromosome 20p12.3-p13 by using DNA chaining study.
Symptoms
The main manifestations are slowly progressive extrapyramidal symptoms, the first symptoms are lower extremity muscle ankylosis, dystonia and choreoathetosis, and early on, there can be cone-bundle sign, spastic paralysis, hyperreflexia, and Babinski’s sign, etc.; gradual progression of the involvement of the upper limbs, the face, and medulla oblongata muscles; some patients have tongue muscle dystonia, blepharospasm, pigmented retinitis, and optic disc atrophy. Dorsiflexion of the body into an arch, causing dysphagia, slurred speech, advanced patients can not get up, most of the patients died within 10 years of the onset of the disease due to complications.
Examination
1. CT examination
It shows enlarged ventricles, obviously enlarged lateral fissure, enlarged sulcus, cerebellar atrophy, etc.; low-density foci of striatum can be seen, and high-density foci have also been reported.
2.MRI examination
T2WI shows low signal in the outer part of both pallidum and small high signal in the inner part of the pallidum, which is called “tiger’s eye sign”.
3. Giemsa-Wright staining of bone marrow macrophages and peripheral blood lymphocytes.
In the Giemsa-Wright staining, navy blue histiocytes can be found, which have PAS-positive fluorescent material in the light under the microscope at 340nm wavelength, which has diagnostic significance.
4. Intravenous injection of 59Fe-labeled iron salt (ferrous citrate)
SPECT imaging shows increased aggregation in the basal basal area, which is delayed in fading compared to normal, which also has diagnostic reference value.
Diagnosis
The diagnosis is based on the presence of progressive extrapyramidal symptoms, dystonia, myotonia, and spastic paralysis of both lower limbs in adolescence, and the typical “tiger’s eye sign” on MRI T2WI.
A positive family history, the presence of navy blue histiocytes in bone marrow macrophages or peripheral blood lymphocytes, or the presence of radioactive accumulation and slow disappearance of 59Fe-labeled iron salts in the bilateral basal nuclei on SPECT imaging, can confirm the disease.
Complications
It may be complicated by primary optic atrophy, psychiatric symptoms, mental decline and recession, ataxia, and epileptic seizures.
Treatment
At present, there is no specific treatment for this disease, and the main treatment is symptomatic. Parkinson’s syndrome with increased dystonia and bradykinesia can be temporarily relieved with levodopa; choreoathetosis can be treated with benzodiazepines; antidepressants can improve the patient’s mood; epileptic seizures can be treated with antiepileptic drugs; neurotrophic drugs are not effective, and chelating agents are ineffective in removing the iron deposition in the basal nuclei.
Vitamin E-rich foods and high-dose vitamin E therapy have been tried, as well as monoamine oxidase-β inhibitors, but the effect is not obvious.
Prognosis
The childhood form of the disease lasts about 10 years, with most dying of complications in their 20s and 30s. The adult form can also last up to 10 years or more.