From Cerebellar Apoplexy in 1849 to Cerebellar Stroke in the 2020s: Robert Dunn's Contribution.

Stroke of the cerebellum represents about 10% of strokes of the brain. Both infarction and hemorrhage manifest with symptoms related to the location and extent of the lesion(s). Bilateral cerebellar infarcts constitute up to one third of all cerebellar infarctions. The leading cause of cerebellar infarcts is emboli of cardiac origin or from intra-arterial sources. Potential complications include brainstem compression and hydrocephalus. Malignant cerebellar edema is a life-threatening complication of ischemic posterior circulation stroke requiring urgent management. The advent of MRI has revolutionized the early diagnosis in vivo, showing small and large territorial infarcts, hemorrhages, and venous infarcts. Endovascular procedures are growingly applied and are impacting on the prognosis of stroke, although cerebellar stroke from occlusion of small cerebellar arteries is currently not accessible to thrombectomy. Surgical procedures of space-occupying stroke include external ventricular drainage, suboccipital craniotomy, or combined procedures. In 1849, Robert Dunn (1799-1877), an English surgeon, reported the details of a case of apoplexy of the cerebellum in a 52-year-old man, pointing to the importance of post-mortem studies of patients followed meticulously during lifetime. Dunn discussed inflammation surrounding hemorrhage as a source of cerebral degeneration, linking for the first time cerebellar stroke, neuroinflammation, and atherosclerosis.

Cerebellar mutism.

Mutism of cerebellar origin is a well-described clinical entity that complicates operations for posterior fossa tumors, especially in children. This review focuses on the current understanding of principal pathophysiological aspects and risk factors, epidemiology, clinical characteristics, treatment strategies, and outcome considerations. The PubMed database was searched using the term cerebellar mutism and relevant definitions to identify publications in the English-language literature. Pertinent publications were selected from the reference lists of the previously identified articles. Over the last few years an increasing number of prospective studies and reviews have provided valuable information regarding the cerebellar mutism syndrome. Importantly, the clarification of principal terminology that surrounds the wide clinical spectrum of the syndrome results in more focused research and more effective identification of this entity. In children who undergo surgery for medulloblastoma the incidence of cerebellar mutism syndrome was reported to be 24%, and significant risk factors so far are brainstem involvement and midline location of the tumor. The dentate-thalamo-cortical tracts and lesions that affect their integrity are considered significant pathophysiological issues, especially the tract that originates in the right cerebellar hemisphere. Moderate and severe forms of the cerebellar mutism syndrome are the most frequent types during the initial presentation, and the overall neurocognitive outcome is not as favorable as thought in the earlier publications. Advanced neuroimaging techniques could contribute to identification of high-risk patients preoperatively and allow for more effective surgical planning that should focus on maximal tumor resection with minimal risk to important neural structures. Properly designed multicenter trials are needed to provide stronger evidence regarding effective prevention of cerebellar mutism and the best therapeutic approaches for such patients with a combination of pharmacological agents and multidisciplinary speech and behavior augmentation.

Nutritional cerebellar degeneration, with comments on its relationship to Wernicke disease and alcoholism.

Nutritional cerebellar degeneration occurs in alcoholism and other states that predispose to malnutrition, such as gastric bypass surgery. Gait ataxia is the principal clinical manifestation. Ataxia of the lower limbs is not uncommon, but upper extremity ataxia and nystagmus are rare. Atrophy of the anterior superior vermis is the primary pathological manifestation in established disease. Typically, the onset is subacute. This cerebellar disease is part of the spectrum of the Wernicke-Korsakoff syndrome, i.e. the cerebellar manifestation of Wernicke disease. It may occur with other lesions of Wernicke disease or in isolation. Rarely, with florid disease, lesions may be hemorrhagic. Active disease should be treated with thiamine in the same way that one treats Wernicke disease. Clinicopathologic correlation in this disease has provided the best evidence that the anterior superior vermis is important in coordinating bipedal locomotion.

Cerebellar research: two centuries of discoveries.

Numerous laboratories currently focus their activities on cerebellar research. The cerebellum is attractive due to its sophisticated circuitry, high degree of modifiability combined with unique operational mechanisms, and the growing awareness of its multiple roles. Works of pioneers of these last two centuries, such as Rolando, Flourens, Magendie, Luciani, Lugaro, Babinski, Holmes, Cajal, Larsell, Eccles, Voogd, Llinas, or Ito, still exert a strong influence in the way we investigate cerebellar functions. The amount of knowledge is exploding, thanks to advances in genetics, molecular and cellular analyses, profusion of brain imaging techniques, novel behavioral assessments, and reshaping of models of cerebellar function. More than ever, strong and consistent intellectual efforts are required to generate homogeneous research outcomes that might exert a significant influence in the forthcoming domains of research. Because research is often based on the results of our predecessors, The Cerebellum has launched a section called Cerebellar Classics. Papers selected represent key steps for the discovery of some of the secrets of the cerebellar circuitry. These seminal contributions offer a portal to the past to modern scholars.

Cerebellum: history.

This paper will outline the history of study of the cerebellum from its beginnings to relatively recent times. Although there is no unanimous agreement about what the cerebellum does or how it does it, some principles of its structure and function are well understood. The historical approach can help to identify remaining questions and point the way to future progress. We make no effort to separate anatomical, physiological and clinical studies; rather, we hope to emphasize their interrelation. The cerebellum has always been seen as a distinct subdivision of the brain. Over the years there was an increasingly accurate description of its gross appearance and major subdivisions. By the beginning of the 19th century, the classical descriptive anatomical work was completed, and experimental study of the functions of the cerebellum began. Lesions were made in the cerebellum of experimental animals, and the behavioral deficits that were caused by the lesion were studied and described. These early animal studies powerfully influenced clinical interpretation of the symptoms seen in patients with cerebellar disease. Several questions are implicit in the anatomical and clinical studies of the nineteenth and early twentieth centuries, some of which remain incompletely answered. Many of these are addressed in other chapters in this volume. 1. Do different parts of the cerebellum do different things? The uniformity of the neuronal architecture of the cerebellar cortex suggests that each small region must operate in a similar way, but it is also clear that different regions control different functions. Is there a systematic sensory and/or body representation? 2. What are the functions of the cerebellar hemispheres? Massive in humans and very large in primates, their functions remain in dispute. Because the size of the cerebellar hemispheres parallels the development of the cerebral cortex, some have suggested that the hemispheres in humans and the higher primates may play a role in cognitive functions. 3. If one part of the cerebellum is damaged, can another part take over? A related question is whether normal motor function is possible in cases of complete or near-complete agenesis of the cerebellum. 4. What are the functions of the two distinctly different afferent systems to the cerebellum; the climbing and mossy fibers?

The cerebellum, cerebellar disorders, and cerebellar research--two centuries of discoveries.

Research on the cerebellum is evolving rapidly. The exquisiteness of the cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach cerebellar functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of cerebellar function are generating an immense amount of knowledge. Simultaneously, a better definition of cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of cerebellar function. Contributions were brought together around five themes: (1) cerebellar development, death, and regeneration; (2) cerebellar circuitry: processing and function; (3) mechanisms of cerebellar plasticity and learning; (4) cerebellar function: timing, prediction, and/or coordination?; (5) anatomical and disease perspectives on cerebellar function.

The history of the development of the cerebellar examination.

The cerebellar examination evolved from observations of experimental lesions made by neurophysiologists and clinical descriptions of patients with trauma to the cerebellum. At the beginning of the 19th century, neurophysiologists such as Luigi Rolando, Marie-Jean-Pierre Flourens, and John Call Dalton, Jr. ablated portions of the cerebellum of a variety of animals and observed staggering gait, clumsiness, and falling from side to side without loss of strength. They concluded that the cerebellum coordinated voluntary movements. In 1899, Joseph Francois Félix Babinski observed that patients with cerebellar lesions could not execute complex movements without breaking down into their elemental movements and described the defect as dysmetria. In 1902, Babinski coined the term dysdiodochokinesis to describe the inability to perform rapid execution of movements requiring alternate contractions of agonist and antagonist muscles. Gordon Holmes in 1904 described the phenomena of rebound, noting that if a limb ipsilateral to a cerebellar lesion is suddenly released from tension, the appendage will flail. In 1917, Gordon Holmes reported hypotonia and dysmetria in men wounded by gunshot wounds to their cerebellum. These observations were rapidly included in descriptions of the cerebellar examination in popular contemporaneous textbooks of neurology. Modern observations have demonstrated that the cerebellum influences such cognitive functions such as planning, verbal fluency, abstract reasoning, prosody, and use of correct grammar.

[Cerebellar atrophies]. / Les atrophies cérébelleuses.

The concept of cerebellar atrophy was first introduced by Pierre Marie in 1893 in his description of hereditary cerebellar ataxia. Subsequent criticism of this notion was refuted by the report of new clinicopathological entities which are compatible with it. The contributions of the Clinic for Diseases of the Nervous System are discussed in this paper. Etiological classification is difficult, in spite of progress made in the genetic, epidemiologic, and biochemical approaches to cerebellar atrophies. Pathologic findings appear to supply the most secure basis for presentation of these affections. Predominantly cortical atrophies may be localized to the vermis. This is the case in the familial cerebello-olivary atrophy of Holmes (1907), in tardive cortical atrophy (Pierre Marie, Foix and Alajouanine, 1922), and in the cerebellar atrophy of alcoholics (Alajouanine, Castaigne, Contamin and Lebourges, 1959; Victor, Adams and Mancall, 1959), in which the lesions are similar. The frequent intrication of the various etiological factors: age, deficiencies, alcohol, heredity, suggests the role of a sometimes primary, sometimes latent genetic predisposition, revealed during various pathological conditions. Cortical cerebellar atrophy may be of the diffuse type, as in paraneoplastic cerebellar atrophy (Brouwer and Biemond, 1938), which is closely related to subacute polioencephalomyelitis in cancer patients (Dubas et al., 1982), and in congenital atrophy of the granular layer (Norman, 1940), which is more a dysgenesis than a true degenerative affection. Lesions affecting mainly the efferent or afferent cerebellar pathways include olivopontocerebellar atrophy (Dejerine and André Thomas, 1900) which should be included in the larger overall concept of multiple system atrophy (Oppenheimer, 1976), and dentorubric atrophy (Ramsay Hunt, 1921) which themselves should be integrated in the group of spinocerebellar atrophies. Finally, olivorubrocerebellar atrophy (Lejonne and Lhermitte, 1909) and crossed cerebellar atrophy, traditionally studied together with cerebellar atrophies, are only the result of a pre-existing lesion.

Chronic mania in childhood: case report of a possible association with a radiological picture of cerebellar disease.

The case-history of a woman with psychiatric symptoms since childhood is reported, the best label for which was that of "chronic mania". Cerebellar atrophy was suspected on radiological grounds. The literature on chronic mania in childhood and on cerebellar damage and mental changes is reviewed and the view is put forward that cerebellar dysfunction may play a part in the production of some psychiatric symptoms.