A case of chorea, epilepsy and cerebral atrophy in the work of Ettore Ravenna (1920s)

This study re-examines a rare neuropathological case documented by Ettore Ravenna in 1900, involving a young patient with chorea, epilepsy, and marked frontal lobe atrophy. Using Ravenna’s original autopsy notes and the preserved anatomical preparation at the Morgagni Museum of Human Anatomy (Padua), the case is reassessed in light of modern neurological knowledge. Macroscopic examination confirmed severe anterior frontal atrophy with relative preservation of peri-Sylvian regions, consistent with the patient’s ability to sing despite profound language impairment. Ravenna described gliosis, fibrotic tissue replacement, and neuronal hyaline degeneration, interpreted as ulegyria of inflammatory origin. Although he considered epilepsy and chorea expressions of a single pathology, current research differentiates their mechanisms. However, juvenile neurodegenerative disorders such as Huntington disease show overlapping seizures, chorea, and cortical atrophy, partially supporting his observations. Re-evaluating this case highlights its historical relevance and the value of anatomical collections in reassessing early diagnoses.

Introduction

Ettore Ravenna (1876–1943) was an Italian pathologist and neuropathologist at the University of Padua, known for his studies on chorea, epilepsy, and cortical degeneration (Fig. 1). His work bridges late 19th-century morphological neuropathology and early functional interpretations of neurological disease. Though his career was affected by Fascist racial laws in 1938, his scientific contributions remain significant to the development of Italian neuropathology^1,2.

Ravenna produced numerous clinical and autopsy reports that significantly advanced the understanding of neurological and systemic diseases. Several of the pathological specimens he described are still preserved today in the Morgagni Museum of Human Anatomy in Padua^3,4,5.

During his early research at the University of Padua, where he served as assistant to Prof. Augusto Bonome (1857-1922), Ravenna conducted pioneering analyses of neurological cases. This work enabled him to correlate clinical symptoms with cerebral pathology and to identify the anatomical localization of cortical abnormalities, as demonstrated in his notable case of frontal cerebral atrophy in a young patient presenting with choreic and epileptic symptoms⁶.

A CASE OF CEREBRAL ATROPHY IN A YOUNG PATIENT WITH CHOREIC AND EPILEPTIC SYMPTOMS

Ettore Ravenna conducted the autopsy of a 16-year-old girl who died in 1900 during an epileptic episode. The patient had never developed verbal or linguistic skills, exhibiting persistent deficits in both language production and comprehension. In contrast, musicality and singing abilities were well developed. Her motor behavior was characterised by continuous movements of the limbs and repetitive antero-posterior and lateral oscillations of the trunk and head. Facial observations included grimacing, lip contortions, forehead wrinkling, and protrusion of the tongue.

At the age of 13 years, in 1897, the patient experienced her first epileptic episode, described as a convulsive seizure preceded by a cry and followed by salivation and urinary incontinence. Seizures recurred over the following years and ultimately resulted in her death in 1900⁶.

The autopsy was conducted meticulously, revealing no abnormalities in the heart, lungs, stomach, or intestines. The liver and gallbladder were mildly enlarged. A detailed macroscopic and microscopic examination of the brain was then performed.

The analysis of the cerebral tissues was performed both macroscopically and microscopically.

MACROSCOPIC EXAMINATION

The frontal lobes appeared partially atrophic, with a clear demarcation between healthy and abnormal tissue. Ravenna noted that the anterior portions of both frontal lobes exhibited markedly reduced gyral thickness (1-2 mm) and global cortical atrophy, resulting in a rounded appearance of the cerebral mass due to reduction of the antero-posterior diameter. In contrast, the posterior frontal gyri measured approximately 11 mm in thickness, consistent with normal morphology. Broca’s area (posterior inferior frontal gyrus) and Wernicke’s area (superior temporal gyrus) were therefore spared, accounting for the preservation of the patient’s singing ability⁶.

The brain is currently preserved as a wet anatomical preparation in the Pathological Anatomy section of the Morgagni Museum of Human Anatomy, University of Padua. The reduced thickness of the anterior frontal lobes remains clearly visible. Due to conservation constraints, the specimen cannot be removed from its historical glass jar; thus, high-resolution photographs were acquired through the liquid medium using diffuse cross-polarized lighting and a neutral background to minimise glare and distortion while ensuring adherence to conservation standards (Fig. 2).

MICROSCOPIC EXAMINATION

Histological examination using the Weigert method revealed an atypical pattern characterised by predominance of fibrotic tissue in both gray and white matter, arranged in diverging longitudinal bundles. This pattern was most pronounced in the anterior frontal regions, corresponding to areas of macroscopic atrophy.

Although the posterior frontal regions appeared normal on gross inspection, microscopic analysis revealed degeneration: neuronal protoplasm exhibited hyaline change, and nuclei were intensely stained with thionine. Additional microscopic findings included diffuse cortical atrophy with reduced neuronal density, gliosis and fibrotic replacement of the neuropil.

Areas of hyaline degeneration were observed within the perivascular stroma, particularly in the frontal lobe. The subcortical white matter exhibited rarefaction and vascular proliferation. No evidence of inflammatory infiltrates or calcifications was noted.

Although Ravenna did not provide microphotographs, these descriptions align with chronic cortical atrophy secondary to neurodegenerative or epileptogenic processes.

Ravenna correlated these pathological findings with the clinical presentation: severe cognitive impairment corresponded to anterior frontal atrophy, whereas relative preservation of motor function (including the organization of choreic and epileptic movements) reflected milder involvement of the cortico-motor regions.

PATHOGENETIC INTERPRETATION

Ravenna hypothesised an inflammatory origin for the lesion, suggesting that a long-standing pathological process progressively extended, ultimately precipitating the fatal epileptic episode. He diagnosed the condition as ulegyria, a form of microgyria resulting from chronic inflammatory damage leading to scarring and cortical thinning. Supporting this interpretation, he noted “deep and diffuse gliosis and loss of neural elements in the atrophic area of the frontal lobe; hyaline degeneration of the protoplasm and atrophy of the nucleus of the nerve cells in the non-atrophic area of the frontal gyri”⁶.

Discussion

Ravenna’s description of chronic cerebral atrophy with choreiform movements reflects the scientific vocabulary of early 20th-century Italian neuropathology, at a time when histopathological correlations of movement disorders were still poorly defined. Terminology such as “hyaline degeneration” and “fibrotic substitution” was used descriptively, predating modern concepts such as selective neuronal vulnerability. In light of contemporary neuropathological understanding, the lesions described may correspond to cortical atrophy secondary to repeated epileptic discharges or to neurodegenerative mechanisms similar to those later recognized in Huntington’s disease. The study of such historical specimens therefore provides a unique opportunity to trace the evolution of neuropathological terminology and diagnostic reasoning. Despite the limitations of early microscopy, Ravenna’s work demonstrates a notable attempt to integrate morphology with clinical observation, a methodological foundation that continues to shape modern neuropathology.

The mechanisms underlying the co-occurrence and progression of epileptic and choreic symptoms are still not fully understood today. Historically, chorea and epilepsy were believed to share a common etiology, with chorea considered a milder expression of the same pathological process. Seizures, defined as involuntary muscular contractions accompanied by altered consciousness, result from abnormal, excessive, synchronous neuronal activity within the cerebral cortex. In contrast, chorea consists of involuntary, irregular, non-rhythmic movements arising primarily from dysfunction of the basal ganglia, particularly the striatum (caudate nucleus and putamen). Although basal ganglia disturbances may influence motor cortical activity, cortical pathology is not the primary driver of chorea⁷. Consequently, current neurophysiological models consider the two conditions as having distinct origins.

Therefore, nowadays the etiology of the two pathologies is considered distinct. Nevertheless, the case described by Ettore Ravenna is unique in its kind and offers the opportunity to further investigate the connection between epileptic and choreic symptoms, and how these may evolve from one another. The most similar findings that correspond to Ravenna’s research, both in clinical manifestation and histological findings, are offered by the analysis conducted on four patients with clinical and molecular diagnosis of juvenile or childhood Huntington disease. Clinical features included: choreiform movements, dystonia, cognitive or emotional changes, altered social behavior, with a rather progressive decline. Two other important clinical features were seizures and ataxia. The MRI findings revealed early cortical atrophy and cerebellar volume loss, thereby corroborating Ravenna’s histological conclusions⁸.

Ravenna attributed the patient’s neurological deterioration to an inflammatory process, although he was unable to further specify its nature. Today, frontal lobe dysfunction is known to result from diverse causes, including trauma, neoplasia, hemorrhages, and chronic epilepsy. Given that the cortical structures were examined only post-mortem, epilepsy itself must be considered a plausible contributor to the observed atrophy⁹.

A notable aspect of the clinical history is the parents’ report that the child experienced intense fear at 9 months of age when startled by two approaching bovines, an event they believed triggered the onset of choreic movements. Modern studies demonstrate that seizures may indeed be precipitated by startle responses, including visual, auditory, or somatosensory stimuli. Startle-provoked epileptic seizures (SPES) may occur as isolated episodes or as part of a persistent epilepsy syndrome. A CT-based analysis of 19 SPES patients revealed that such seizures are frequently associated with occult congenital lesions and that the lateral premotor cortex plays a key role in their pathophysiology¹⁰. Thus, Ravenna’s case may reasonably be interpreted as multifactorial, involving both environmental triggers and a possible congenital predisposition.

Conclusion

The re-evaluation of Ravenna’s early 20th-century case of chorea, epilepsy, and frontal cortical atrophy underscores the enduring value of historical neuropathological documentation. Although modern neurology recognizes that chorea and epilepsy arise from distinct pathophysiological mechanisms, this case illustrates how careful clinical observation and systematic autopsy interpretation allowed Ravenna to anticipate complex associations that are still discussed today. Epileptic manifestations are not frequently linked to choreic symptoms; however, contemporary literature confirms that, when the full clinical course is reconstructed, overlapping presentations may occur in conditions such as juvenile Huntington disease or startle-provoked epilepsy.

Ravenna’s meticulous reconstruction of the patient’s neurological history combined with detailed macroscopic and microscopic examination represents one of the earliest attempts in Italian neuropathology to correlate behavioral symptoms, motor disturbances, and focal cortical degeneration. This retrospective analysis highlights the transition from a purely morphological approach to a proto-functional interpretation of neurological disease.

Furthermore, the present study demonstrates how museum-held pathological preparations, when re-examined through a modern lens, can yield new insights into the evolution of diagnostic reasoning and the historical foundations of movement-disorder neuropathology. The Morgagni Museum specimen remains a valuable resource for both historians of medicine and contemporary neuroscientists, illustrating the scientific importance of preserving and reassessing historical anatomical collections.

ACKNOWLEDGEMENTS

None

CONFLICTS OF INTEREST

All authors have no conflict of interest to report.

FUNDING

No funding to declare

AUTHORS’ CONTRIBUTIONS

GM: Conceptualization; Methodology; Formal analysis and investigation; Writing - review and editing: Supervision. IK: Conceptualization; Methodology; Formal analysis and investigation; Writing - original draft preparation; Writing - review and editing. AZ: Writing - review and editing: Supervision

ETHICAL CONSIDERATION

Not applicable.

History

Received: November 27, 2025

Accepted: December 24, 2025

Figures and tables

Figure 1. Ettore Ravenna in his elderly years.

Figure 2. a) Anatomical preparation of the case studied by Ettore Ravenna preserved in liquid at the Morgagni Museum; b) Detail of the specimen, showing the frontal atrophy. © Giovanni Magno - University of Padua.