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Data presented during a session at the French Language Neurology Days 2026 highlighted the importance of considering toxic exposure in the differential diagnosis of several neurologic disorders, including leukoencephalopathy, stroke, and demyelinating disease.

The findings were presented by Alexander Balcerac, MD, Department of Neurology, Hôpital de la Pitié‑Salpêtrière, Sorbonne Université, Assistance Publique - Hopitaux de Paris, Sorbonne Université, Paris; Stéphane Kreme r MD, PhD, professor and head of the Imaging Department at the Les Hôpitaux Universitaires de Strasbourg; Loïc Benefice, MD, Neurology, HIA Sainte‑ Anne (Hôpital d'Instruction des Armées Sainte‑Anne), in Toulon, France; and  Daniel Bequet, MD, neurologist practicing in Garches  and former professeur agrégé , service de Neurologie Hôpital d'Instruction des Armées du Val-de-Grâce Paris. 

The speakers described several neurologic injury patterns that may help clinicians identify specific classes of toxic substances.

1. Leukoencephalopathy involving both the corpus callosum and dentate nuclei or dentate gyrus, regions considered particularly vulnerable to oxidative stress. This damage pattern is commonly observed:

• While receiving metronidazole or high dose methotrexate
• During occupational exposure to nitrobenzene and methyl iodide
• In agricultural settings involving fertilizer exposure

It is typically observed during chronic exposure to toluene-based paint solvents and heroin inhalation.

• Damage involving the corpus callosum and cerebellar peduncles has also been associated with exposure to 5-fluorouracil and its precursor capecitabine. Other less specific clinical presentations may be observed.
• Posterior reversible encephalopathy syndrome may have the following causes:
• Drug related (eg, cytotoxic chemotherapy, immunosuppressants)
• Nonpharmacological causes such as venoms, organophosphates, illicit drugs such as amphetamines, cocaine
• Poisoning from lead or arsenic
• Cytotoxic lesions of the corpus callosum have also been associated with weight loss and thermogenic products.
• Disorders of the basal ganglia. This may be related to the following findings:
• Symmetrical involvement of the lenticular nuclei (putamen and globus pallidus). These findings are seen in osmotic encephalopathies and poisoning from organophosphates and toxic alcohols, such as methanol and ethylene glycol.
• Lesions involving the globus pallidus and dentate nuclei with hypersignals in these regions. These findings are associated with metal deposition, including manganese linked to portosystemic shunts or parenteral nutrition, gadolinium after repeated exposure, and chromium or cobalt from prosthetic wear.
• Damage to the globus pallidus, a region with a limited blood supply, which is particularly vulnerable to toxins that inhibit oxidative phosphorylation, including carbon monoxide, cyanide, and neonatal hyperbilirubinemia.

The lesions may involve the following regions:

• The anterior cingulate cortex and insula. These findings are associated with acute hyperammonemic encephalopathies related to drug poisoning, particularly valproic acid poisoning.
• Predominantly cortical lesions. These are associated with hypoglycemia.
• Corticosubcortical lesions. These findings correspond to anoxic ischemic encephalopathies caused by carbon monoxide or cyanide poisoning.

The radiological presentation of poisoning varies widely. The distribution of findings depends on the physicochemical properties of the toxins and their mechanisms of action. Brain imaging plays a central role but should not be interpreted alone. Findings should always be considered alongside clinical and laboratory data, as well as the patient's medical history.

One particularly challenging diagnosis discussed during the session was levamisole-associated inflammatory leukoencephalopathy, often linked to cocaine use. This condition closely resembles multiple sclerosis. Patients may present with acute confusion, behavioral changes, impaired consciousness, and focal neurologic deficits with rapid clinical progression.

MRI findings show:

• Predominant involvement of deep white matter
• Sparing of the subcortical U-fibers
• Frontoparietal and periventricular distribution
• Minimal cortical or ventricular involvement

Features favoring differential diagnosis of multiple sclerosis include: 

• Venocentric lesions
• Spinal cord involvement
• Appearance of new distant lesions over time

Toxic exposure may also contribute to cerebrovascular disease, particularly among younger adults. An increasing number of reports of stroke in younger populations are potentially linked to recreational drug use. 

Several toxic substances have been linked to vascular events.

• Cocaine has primarily been associated with hemorrhagic stroke.
• Amphetamines with stroke and small vessel injury in regular users;
• Nitrous oxide with cerebral venous thrombosis and ischemic stroke;
• Emerging data also suggest a possible association with alkyl nitrites, commonly known as poppers.

The diagnosis is based on the following:

• Detailed interviews are often limited by underreporting.
• Toxicological tests whose sensitivity depends on the time elapsed since sample collection;
• Ideally, early screening is performed upon admission.

Toxicological evidence can sometimes be difficult to establish.

A definitive diagnosis of poisoning remains a major challenge. Historical data on arsenic poisoning illustrate the difficulties in interpreting toxicological analyses, with controversies linked to environmental contamination and the limitations of analytical methods.

Although advances in analytical techniques now allow highly sensitive detection of toxic substances, interpreting the findings remains complex for several reasons:

• Detecting a toxic substance does not always confirm that it is the cause of the symptoms.
• Concentrations may be low or can only be identified after a delay.
• Environmental factors may interfere with the interpretation.

This story was translated from Univadis France, part of the Medscape Professional Network.