Spongiform leukoencephalopathy after heroin abuse
05 November 2004
Heroin is the diacetyl derivative of morphine. The usual route of administration is intravenous; other methods include intramuscular, subcutaneous, rectal and intranasal. After absorption, it is rapidly converted into either morphine or MAM (monoacetylmorphine) which is highly lipid soluble allowing good penetration through the blood brain barrier to cause morphine euphoria or a “high”. It is purchased on the blackmarket and often contaminated.
The neurologic complications of this illegal substance are numerous: plexopathies, nerve pressure palsies, hypoxic encephalopathy, seizures, rhabdomyolysis, transverse myelopathies, abscesses and vasculitis. One rare complication of heroin abuse is spongiform leukoencephalopathy, which is most often associated with the intranasal route of administration known as “chasing the dragon” or “chinesing” and reported most frequently in the Netherlands. Chasing the dragon is performed by heating heroin on a tin foil with a lighter and inhaling the fumes.
The first reports of heroin causing spongiform leukoencephalopathy were in 1982 pertaining to a group of users in Amsterdam. To date there are only approximately 70 reported cases of this rare complication in worldwide literature with about 60 reports from Amsterdam and several other reports from Italy, Germany, US and one from Taiwan. There have been no such reports from Australia to our knowledge.
A 38 year old man was brought into our hospital by a concerned wife with a 6 week history of cognitive impairment, ataxia and motor restlessness. He worked as a furniture removalist; however, he was performing his job poorly where he would be unable to locate the delivery location, drive continuously till his van ran out of petroleum. The police would often assist him but he was unable to tell them his destination, his home address nor why he failed to refuel his vehicle. He was breath tested by the authorities on several occasions and showed no evidence of alcohol; he was not tested for other substances.
Information by the patient, his wife and police provided evidence that he used several illicit substances including heroin, marijuana and amphetamines. He rarely drank alcohol but smoked 1 packet of cigarettes per day. The heroin and amphetamines were by the intravenous route. Over the past 6 months, he had used the intranasal route by the method described above on approximately 5 occasions but found the experience less enjoyable compared to the intravenous route. His wife used similar illicit substances with similar methods but was well. Other past history included hepatitis C not complicated by cirrhosis. There was no family history of neurological, metabolic nor psychiatric disease.
At the hospital, he was unable to recall the date, home address but could remember his age, date of birth, recognise his wife and recall the name of his children. He walked with an ataxic gait and there was dysmetria in both upper & lower limbs. Bilateral horizontal gaze nystagmus was present. During his stay in hospital, he displayed motor restlessness, both ideational and ideomotor apraxia and was seen using alcohol and injecting heroin.
Investigation revealed normal blood counts, electrolytes, clotting profile, serum lactate and pyruvate. Serology was negative for HIV, syphilis, ANA, extractable nuclear antigens, lupus anticoagulant, anticardiolipin and rheumatoid factor. A lumbar puncture was performed which revealed an opening pressure of 12 cm water. CSF showed protein 305 mg/l, glucose 3.4 mmol/l (simultaneous serum glucose 5.0 mmol/l ), 1 white cell x 106 /l, 15 red cells x 106 /l and unremarkable cytology. RPR & TPHA, HSV PCR and brain protein 14-3-3 performed on the CSF were negative. CT of brain showed marked periventricular hypodense changes. The MRI revealed marked periventricular hyperintenisty on T2 and hypointensity on T1. A brain biopsy was performed of the involved area of R frontal region seen on MRI. During the biopsy procedure, the neurosurgeon noted that the brain appeared to be atrophied with reduced surface convolutions. The tissue was noted to be quite granular and friable. The light microscopy showed abnormal white matter with patchy spongiform change and prominent reactive fibrous gliosis consisting of GFAP positive fibrous astrocytes.
The patient subsequently absconded and no followup could be arranged. One and half months later he was apprehended for drug trafficking in another state. After discussion with the police surgeon, it appears his condition has improved with nonataxic gait, no nystagmus, normal speech but mildly reduced cognitive function.
Our patient had cognitive dysfunction, cerebellar ataxia, dysarthria, motor restlessness with radiological findings of hypodensities in the cerebral and cerebellar white matter on CT, and even more pronounced findings at the same sites on MRI with hyperintenisty on T2 and hypointensity on T1. In conjunction with the right frontal lobe white matter brain biopsy showing spongiosis, we believe this man suffered from heroin related spongiform leukoencephalopathy.
Diseases such as Schilder’s disease, Canavan’s disease, adrenoleukodystrophies and mitochondrial disease were considered unlikely given the age of onset, normal serum pyruvate and serum lactate, absence of family history, lack of systemic manifestations and changes seen on CT and MRI.
The mortality rate is about 25 % with heroin related spongiform leukoencephalopathy. Three stages of this disease are described. The initial stage consisted primarily of soft speech, cerebellar ataxia, motor restlessness and apathy. Intermediate stage showed evidence of pyramidal tract lesions, pseudobulbar reflexes, spastic paresis, tremor, myoclonic jerks and choreoathetoid movements. In the terminal stages, there are stretching spasms, hypotonic paresis, akinetic mutism and central pyrexia. We believe our patients had features of the initial stages of heroin encephalopathy.
There is characteristic neuropathology. LM showed spongifrom degeneration of white matter in all cases with occasional foci of necrosis. EM showed vacuolar degeneration of the oligodendroglia, swollen mitochondria and distended endoplasmic reticulum. Neuropathological findings reveal involvement in order of frequency: the white matter of cerebral hemispheres, cerebellar white matter, superior cerebellar peduncles, medial longitudinal fasciculus, truncus corticospinalis, lemniscus medialis, truncus solitarius, vestibular nerves, fasciculus gracilis and cuneatus, sural nerve. MRI findings on our patient showed lesions in cerebral and cerebellar white matter.
The exact substance that causes this unusual encephalopathy is unknown. The difficulty lies in there being so much variability in the purity and type of contaminants in these illicit substances. Spongiform encephalopathy has not been reported with marijuana and amphetamine usage.
Analytical studies have been performed on illicit heroin and the products formed by volatising heroin (the method used in chasing the dragon). Common contaminants include ascorbic acid, cocaine base, colophonium, glucose, lactose, mannitol, caffeine, strychnine, methaqualone, nicotinamid, paracetamol, phenazone, and piracetam. None of these substances have been reported to cause spongiform leukoencephalopathy. After heating on a tin foil, heroin pyrosylate fumes are formed and subsequently inhaled. Analysis of these fumes have also failed to find a substance that could cause spongiform encephalopathy.
Apart from an environmental agent, there must be an individual predisposition to this heroin related complication. His wife shared illicit substances with him and used these in a similar fashion but suffered no medical complications apart from hepatitis C. In other reports, users of the same batch of heroin as those who developed spongiform leukoencephalopathy suffered no consequences.
Illicit heroin use is prominent in Australia, particularly in our larger cities and lower socioeconomic classes. Chasing the dragon has a major advantage over the intravenous route in avoiding transmission of infectious diseases. However, it does subject the user to this rare, disabling and potentially fatal complication of spongiform leukoencephalopathy. This condition is probably underrecognised. The clinical features with characteristic neuroradiological findings should alert the clinician about the diagnosis. The toxic agent and predisposing factors in the individual are yet to be delineated.