Chronic Cocaine Use Linked to Rare Baló-Like Concentric Leukoencephalopathy

Cocaine-Induced Neurotoxicity and the Spectrum of Leukoencephalopathy

The clinical landscape of substance-induced neurotoxicity is expanding as physicians encounter increasingly diverse presentations of white matter injury. While cocaine use is a well-recognized trigger for acute vascular events and posterior reversible encephalopathy syndrome (a clinical-radiological syndrome involving headache, seizures, and altered mental status), its association with complex inflammatory demyelination remains less defined [1]. These toxic leukoencephalopathies, which primarily affect the brain's white matter, often present as diagnostic challenges that mimic the hyperacute onset of cerebrovascular accidents or the aggressive course of tumefactive demyelinating disorders (large, tumor-like inflammatory lesions that can cause significant mass effect) [2]. Beyond the immediate risks of respiratory depression and rhabdomyolysis (the breakdown of muscle fibers leading to the release of myoglobin into the bloodstream), the long-term neurological consequences of chronic stimulant and opioid exposure include progressive white matter degeneration and disrupted antinociceptive networks (the neural pathways responsible for pain modulation) [3, 4, 5, 6]. Distinguishing these toxic insults from primary autoimmune processes is essential for selecting appropriate interventions, such as high-dose corticosteroids or intravenous immunoglobulin, to improve long-term prognosis. A recent study now provides clinical evidence of a rare, concentric pattern of demyelination resembling Baló concentric sclerosis (a progressive variant of multiple sclerosis) in the context of chronic cocaine use [7].

Clinical Presentation of Acute Multifocal Deficits

The researchers identified two distinct cases of acute multifocal leukoencephalopathy with a Baló-like pattern in patients with a documented history of chronic cocaine use. These individuals resided within the same geographic area in an Italian province, spanning approximately 70 miles, raising the possibility of a shared toxic exposure or a common adulterant in the local drug supply. The first patient was a 31-year-old woman originally from the Philippines who presented with a one-week history of rapidly worsening neurological deficits. Her clinical profile was characterized by nonfluent aphasia (difficulty producing speech), neglect (lack of awareness of one side of the body), severe right hemiparesis, and numbness on the same side. Two months after the first case, a 25-year-old man originally from Morocco with a similar history of chronic cocaine use presented with acute neurological deterioration. His symptoms included acute left leg weakness, confusion, and neglect. In both patients, the rapid onset of these multifocal deficits initially suggested a complex inflammatory process rather than a typical vascular event, prompting further diagnostic workup. The temporal and geographic proximity of these presentations, occurring within a two-month window, provided a unique opportunity for the authors to examine the immune mechanisms that drive this rare form of concentric demyelination in the context of stimulant use.

Radiologic and Histopathologic Markers of Baló-Like Demyelination

While cocaine use is occasionally associated with acute leukoencephalopathy, the magnetic resonance imaging (MRI) features of these cases only rarely resemble Baló concentric sclerosis. This condition is a demyelinating disorder traditionally considered within the multiple sclerosis spectrum, characterized by its distinct concentric patterns of myelin loss. In both patients identified in this study, brain MRI revealed multiple T2-hyperintense rounded lesions in the white matter. These lesions were specifically characterized by a concentric target-like appearance, a hallmark of Baló-like pathology that reflects alternating layers of preserved and destroyed myelin. Furthermore, the imaging showed a gadolinium-enhanced incomplete ring pattern, a radiologic sign often associated with active, leading edges of demyelination where the blood-brain barrier has been compromised. To confirm the underlying pathology, the researchers performed a stereotactic biopsy (a minimally invasive procedure using computer guidance to sample brain tissue) on the first patient. The biopsy confirmed a demyelinating inflammatory process, providing definitive evidence of the nature of the white matter injury. Histopathologic analysis revealed microcystic degeneration (the formation of tiny fluid-filled spaces due to tissue breakdown), increased cellularity, and significant macrophage and CD4+ lymphocyte infiltration. The presence of CD4+ lymphocytes, which are helper T cells that coordinate the immune response, alongside macrophages, suggests a robust cell-mediated immune attack against the myelin sheath. For clinicians, these findings provide a cellular basis for the concentric lesions seen on imaging and highlight the inflammatory drive behind this rare presentation of cocaine-induced neurotoxicity, guiding the choice of immunomodulatory therapy.

Management Strategies and Long-Term Outcomes

Although cocaine use is occasionally associated with the development of acute leukoencephalopathy (a disease of the brain white matter characterized by damage to the myelin sheath), the specific Baló-like presentation observed in these patients required a targeted anti-inflammatory approach. To address the acute demyelinating process and the significant macrophage and CD4+ lymphocyte infiltration identified on biopsy, clinicians initiated aggressive immunosuppression. Both patients were treated with high-dose intravenous corticosteroids, a standard intervention for severe inflammatory demyelination intended to stabilize the blood-brain barrier and reduce the localized immune attack on the myelin layers. The clinical response to this intervention was robust in both cases. The researchers reported that the treatment resulted in significant clinical and radiologic improvement sustained at a 1-year follow-up, with both patients maintaining the gains achieved after the initial acute phase. However, the authors underscore that the long-term prognosis hinges on sustained treatment adherence and abstinence from cocaine. For practicing physicians, this underscores the dual necessity of acute immunomodulation and long-term addiction management. Given the temporal and geographic clustering of these cases, continued cocaine use represents a critical risk factor for the recurrence of these rare, concentric white matter lesions.

Geographic Clustering and Potential Toxic Triggers

The occurrence of these two rare cases of Baló-like concentric leukoencephalopathy (a demyelinating disorder characterized by concentric rings of myelin loss and preservation) within a narrow window of time and space suggests an underlying environmental or toxicological driver. The researchers noted that both cases occurred within two months in the same Italian province, covering an area of approximately 70 miles. This high degree of temporal and geographic proximity is highly unusual for such a rare pathology, which is traditionally considered a variant within the multiple sclerosis spectrum rather than a typical consequence of substance use. The authors propose that the temporal and geographic proximity suggests the possibility of a shared toxic exposure, potentially involving a specific contaminant or adulterant present in the local cocaine supply. Such a shared trigger might explain the unique pathology observed in these patients and provide clues to the immune mechanisms that drive Baló-like demyelination. While the exact nature of the potential toxin remains unidentified, the clustering of these cases in a 70-mile radius indicates that physicians should maintain a high index of suspicion for atypical inflammatory brain lesions in patients with a history of cocaine use. Recognizing this pattern allows clinicians to expedite MRI screening and initiate high-dose corticosteroids rapidly, potentially mitigating severe neurological deficits.

References

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