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Alessandro Dario, Giuseppe Ottavio Armocida and Davide Locatelli

The authors report the history of the Tabulae Anatomicae of Bartolomeo Eustachio (ca. 1510–1574). In the tables, the anatomical illustrations were drawn inside a numerical frame, with pairs of numbers on the y- and x-axes to identify single anatomical details in the reference table. The measures and the references could be calculated using the graduated margins divided by 5 units for each the x-axis and y-axis. The Tabulae Anatomicae can be considered a precursor to modern anatomical reference systems that are the basis of studies on cerebral localization mainly used for stereotactic procedures.

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Zach Folzenlogen and D. Ryan Ormond

Modern cortical mapping is a cornerstone for safe supratentorial glioma resection in eloquent brain and allows maximal resection with improved functional outcomes. The unlocking of brain functionality through close observation and eventually via cortical stimulation has a fascinating history and was made possible by contributions from early physician-philosophers and neurosurgery’s founding fathers. Without an understanding of brain function and functional localization, none of today’s modern cortical mapping would be possible.

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The Chiari I malformation

JNSPG 75th Anniversary Invited Review Article

Samuel G. McClugage III and W. Jerry Oakes

As with many pathologies, the course of our understanding of the Chiari I malformation (CIM) has developed extensively over time. The early descriptions of the Chiari malformations by Hans Chiari in 1891 opened the door for future classification and research on this topic. However, even over a long timeframe, our understanding of the pathophysiology and, more importantly, treatment, remained in its infancy. As recently as the 1970s, CIM was not discussed in popular neurology textbooks. Syringomyelia is listed as a degenerative disorder with no satisfactory treatment. Radiation therapy was considered an option in treatment, and surgery was thought to play no role. During the last 40 years, equivalent to the duration of a neurosurgical career, our understanding of the pathophysiology and natural history of CIM, coupled with modern MRI, has improved the treatment paradigm for this patient population. More importantly, it has given us evidence confirming that CIM is a disorder responsive to surgical intervention, giving patients once thought to be destined for lifelong disability a comparatively normal life after treatment. The purpose of this article is to offer a review of CIM and its important associated entities. The authors will discuss the evolution in understanding of the Chiari malformation and, importantly, distinguish between symptomatic CIM and asymptomatic tonsillar ectopia, based on imaging and presenting symptomatology. They will discuss techniques for surgical intervention, expected outcomes, and complications after surgery. Proper patient selection for surgery based on appropriate symptomatology is tantamount to achieving good surgical outcomes in this population, separating those who can be helped by surgery from those who are unlikely to improve. While our knowledge of the Chiari malformations continues to improve through the efforts of clinical and basic science researchers, surgeons, and patients, our current understanding of these entities represents a monumental improvement in patient care over a relatively short time period.

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The current state of immunotherapy for gliomas: an eye toward the future

JNSPG 75th Anniversary Invited Review Article

Peter E. Fecci and John H. Sampson

The last decade has seen a crescendo of FDA approvals for immunotherapies against solid tumors, yet glioblastoma remains a prominent holdout. Despite more than 4 decades of work with a wide range of immunotherapeutic modalities targeting glioblastoma, efficacy has been challenging to obtain. Earlier forms of immune-based platforms have now given way to more current approaches, including chimeric antigen receptor T-cells, personalized neoantigen vaccines, oncolytic viruses, and checkpoint blockade. The recent experiences with each, as well as the latest developments and anticipated challenges, are reviewed.

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Carlo Serra, Lelio Guida, Victor E. Staartjes, Niklaus Krayenbühl and Uğur Türe

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.

Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the “thalamus opticorum nervorum”) to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.

Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo.

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Shervin Rahimpour, Michael M. Haglund, Allan H. Friedman and Hugues Duffau

Lesion-symptom correlations shaped the early understanding of cortical localization. The classic Broca-Wernicke model of cortical speech and language organization underwent a paradigm shift in large part due to advances in brain mapping techniques. This initially started by demonstrating that the cortex was excitable. Later, advancements in neuroanesthesia led to awake surgery for epilepsy focus and tumor resection, providing neurosurgeons with a means of studying cortical and subcortical pathways to understand neural architecture and obtain maximal resection while avoiding so-called critical structures. The aim of this historical review is to highlight the essential role of direct electrical stimulation and cortical-subcortical mapping and the advancements it has made to our understanding of speech and language cortical organization. Specifically, using cortical and subcortical mapping, neurosurgeons shifted from a localist view in which the brain is composed of rigid functional modules to one of dynamic and integrative large-scale networks consisting of interconnected cortical subregions.

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Michael Fana, Eleanor C. Smith, Jessica L. Gable, Nihal Manjila and Sunil Manjila

The Nazi regime held power for well over a decade in Germany and were steadfast in their anti-Semitic agenda. Among the massive cohort of immigrants to America were approximately 5056 Jewish physicians, including several highly esteemed neurologists and neuroscientists of the time. Emigrating to a new world proved difficult and provided new challenges by way of language barriers, roadblocks in medical careers, and problems integrating into an alien system of medical training and clinical practice. In this article, the authors examine the tumultuous and accomplished lives of three Jewish German and Austrian neurologists and neuroscientists during the time of the Third Reich who shaped the foundations of neuroanatomy and neuropsychology: Josef Gerstmann, Adolf Wallenberg, and Franz Josef Kallmann. The authors first examine the successful careers of these individuals in Germany and Austria prior to the Third Reich, followed by their journeys to and lives in the United States, to demonstrate the challenges an émigré physician faces for career opportunities and a chance at a new life. This account culminates in a description of these scientists’ eponymous syndromes.

Although their stories are a testimony to the struggles in Nazi Germany, there are intriguing and notable differences in their ages, ideologies, and religious beliefs, which highlight a spectrum of unique circumstances that impacted their success in the United States. Furthermore, in this account the authors bring to light the original syndromic descriptions: Gerstmann discovered contralateral agraphia and acalculia, right-left confusion, and finger agnosia in patients with dominant angular gyrus damage; Wallenberg described a constellation of symptoms in a patient with stenosis of the posterior inferior cerebellar artery; and Kallmann identified an association between hypogonadotropic hypogonadism and anosmia based on family studies. The article also highlights the unresolved confusions and international controversies about these syndromic descriptions. Still, these unique cerebral syndromes continue to fascinate neurologists and neurosurgeons across the world, from residents in training to practicing clinicians and neuroscientists alike.

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Mark C. Preul, Charles Prestigiacomo, T. Forcht Dagi and Javier Fandino

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Rodrigo Carrasco-Moro, Ines Castro-Dufourny, Juan S. Martínez-San Millán, Lidia Cabañes-Martínez and José M. Pascual


Establishing the neurological localization doctrine for the contralateral hemispheric control of motor functions in the second half of the 19th century, researchers faced the challenge of recognizing false localizing signs, in particular paradoxical or ipsilateral hemiparesis (IH). Despite tremendous progress in current methods of neuroradiological and electrophysiological exploration, a complete understanding of this phenomenon has yet to be attained.


The authors researched the well-described cases of hemiparesis/hemiplegia ipsilateral to an intracranial lesion published in the scientific literature in the pre-MRI era (before 1980). A comprehensive review of the physiopathological mechanisms proposed for paradoxical hemiparesis throughout this period, as well as the pathological evidence substantiating them, is provided.


A collection of 75 patients with hemiparesis/hemiplegia ipsilateral to the primary intracranial lesion reported between 1858 and 1979 were eligible for analysis. Most cases occurred in adults with supratentorial, slowly developing, extraparenchymatous mass lesions, such as neoplasms (38%) or chronic subdural hematomas (36%). Physiopathological theories proposed by the neurologists who investigated IH can be grouped into 4 major concepts: 1) lack of anatomical decussation of the corticospinal tract; 2) impaired functional activation of the contralateral hemisphere by the lesioned dominant hemisphere through the callosal connections; 3) Kernohan’s notch phenomenon, or mechanical injury of the contralateral cerebral peduncle against the free edge of the tentorium; and 4) cerebrovascular dysfunction involving the contralateral hemisphere owing to kinking and mechanical flattening of the carotid artery contralateral to the primary intracranial lesion.


IH represents a still underdiagnosed paradoxical neurological phenomenon. With the aid of modern neuroradiological and neurophysiological methods, Kernohan’s peduncle notch mechanism has been confirmed to cause IH in many of the cases reported in recent decades. Nevertheless, alternative functional and/or vascular mechanisms must be investigated further for unexplained IH cases, in particular for transitory IH without evidence of peduncle injury. The historical theories reviewed in this paper represent a conceptual framework that may be helpful for this purpose.