Algumas descrições de caso na Neurologia foram muito importantes, por ajudarem a estabelecer novas teorias sobre o funcionamento do sistema nervoso ou mudarem antigos paradigmas.

Os exemplos mais conhecidos e frequentemente citados são:

	Descrição inicial	Descoberta decorrente da descrição
“Tan“	1861 (Pierre Paul Broca)	Delimitação de área cerebral importante para a linguagem; conceito da lateralização das funções cerebrais
Phineas Gage	1848, 1868, 1869 (John M. Harlow)	Descrição de lesão cerebral como causa de mudanças de comportamento e personalidade
H.M.	1957 (William B. Scoville e Brenda Milner)	Papel das estruturas mediais do lobo temporal na memória
S.M.	1994 (Ralph Adolphs, Daniel Tranel, Hanna Damásio e António R. Damásio)	Elucidação das funções da amígdala

“Tan”

Pierre Paul Broca apresentou, em 1861, o caso de Louis Victor Leborgne (1810-1861) com o resultado de sua autópsia no encontro da Sociedade de Antropologia de Paris. Leborgne foi paciente na Bicêtre de 1840 até seu falecimento em 17/04/1861 devido a uma perda de capacidade de expressão (falada ou escrita) de linguagem, sua comunicação se restringindo a gestos e a várias entonações de uma única sílaba: “tan”.

A biopsy of his brain revealed a large lesion in the frontal area —specifically, in the posterior inferior frontal gyrus, a section that corresponds roughly to Brodmann’s areas 44 and 45. Today, we remember Leborgne as Patient Tan, one of the most famous patients in the history of psychology. And we remember his brain as the brain that was ground zero for Broca’s Area, one of the most widely studied language regions in cognitive psychology.

Just a few months after Leborgne’s death, Broca met Lazare Lelong, an 84-year-old grounds worker who was being treated at Bicêtre for dementia. A year earlier, Lelong had, like Leborgne, largely lost the ability to speak. In contrast to Leborgne’s ever-present tan, however, he retained the ability to say a few words that held real meaning. Five, to be exact: oui (yes), non (no), tois (from trois, or three; Lelong used it to mean any number whatsoever), toujours (always), and Lelo (his attempt to say his own name).

When Lelong died, his brain, too, was autopsied. What Broca found—a lesion that encompassed much the same area as had been affected in Leborgne’s brain—confirmed a suspicion that had been growing ever-stronger in his mind: our speech function was localized. A specific area governed our ability to produce meaningful sounds—and when it was affected, we could lose our ability to communicate. What would remain intact, however, was the rest of our intelligence and language comprehension. Not only was speech function localized, but it could be dissociated into specific areas: comprehension, production, formation. An injury to one part did not necessitate an injury to others.

(KONNIKOVA, 2013.)

E:

…But it wasn’t until 1865, a full four years after the famed Tan autopsy, that Broca was finally ready to assert that speech production was localized in a specific part of the left frontal lobe, the region that now bears his name. By that time, he had described the brains of 25 additional patients who had suffered from aphémie and had come to conclude that speech articulation was indeed controlled by the left frontal lobe, just as Bouillard [Jean-Baptiste Bouillard, docente na Hôpital de la Charité em Paris] and Auburtin [Simon Alexandre E. Auburtin] had suspected.

That wasn’t, however, the whole story.

Brain function wasn’t entirely fixed, Broca wrote. With time — and therapy — individuals could improve. Most aphasiacs, he noted, would within weeks begin to regain some of their abilities, or become better able to function even with their loss – especially if they were given the opportunity to practice. Could it not be, Broca wondered, that the right hemisphere was taking over some of the functions of the left? In this question, Broca went a step beyond anyone who had come before him. He anticipated our current understanding of adult brain plasticity, the ability of the brain to learn new ways of function when old ways were no longer an option.

(Idem.)

^ (Tabela)

Phineas Gage

Apesar de muitos autores citarem a descrição de caso de Phineas Gage (1823-1860) como um exemplo de síndrome do lobo frontal, na verdade a noção da localização das funções encefálicas era ainda objeto de debate. E como não há dados da lesão original — apenas inferências baseadas na provável trajetória da barra de ferro pelo crânio de Gage — e as descrições posteriores não serem tão rigorosas, tudo o que se pode dizer do relato é que a “região” frontal possua algum tipo de influência sobre o comportamento e a personalidade.

O apêndice do artigo de MCMILLAN, 2000, apresenta estas transcrições dos relatos de Harlow:

Pre-Accident

Harlow (1848): Gage was of “vigorous physical organization, temperate habits, and possessed of considerable energy of character.”

Harlow (1868, 1869): Gage was a “perfectly healthy, strong and active young man… possessing an iron will as well as an iron frame; muscular system unusually well-developed – having had scarcely a day’s illness from his childhood.” His temperament was “nervo-bilious,” and he was not given to profanity.
Educationally and psychologically, “although untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation.”
Gage’s contractors then “regarded him as the most efficient and capable foreman in their employ.”

Immediate Post-Accident

Harlow (1868, 1869): In April, 1849 “his physical health is good, and I am inclined to say that he has fully recovered.”

Gage’s mother and brother-in-law (August, 1849): “abt. February he was able to do a little work abt. ye horses & barn, feedg. ye cattle &c.; that as ye time for ploughing came [May or June] he was able to do half a days work after that & bore it well.”
“He was weak and childish on getting home but now appears well in mind, exc. that his memory seems somewhat impaired; a stranger wd notice nothing peculiar.”

Standing Committee on Surgery (1850), Report: “A friend writes us, April 27th., 1850, that it is certain his mental powers are greatly impaired. This is stated by the family to which he belongs, and it is their belief that this degenerating process is still going on. He has also lost bodily powers although this fact is not so clearly manifested as the deficiency of his mental faculties.”

Psychological and Behavioural Changes

Harlow (1868, 1869): “His contractors, who regarded him as the most efficient and capable foreman in their employ previous to his injury, considered the change in his mind so marked that they could not give him his place again. The equilibrium or balance, so to speak, between his intellectual faculties and his animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man. Previous to his injury, although untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage.’”
In summary, “mentally the recovery was only partial, his intellectual faculties being decidedly
impaired, but not totally lost; nothing like dementia, but they were enfeebled in their manifestations, his mental operations being perfect in kind, but not in degree or quantity.”

Subsequent History

Harlow (1868, 1869): “He took to travelling and visited Boston, and most of the larger New England towns, and New York, remaining awhile in the latter place at Barnum’s with his iron. 1851 he engaged with Mr. Jonathan Currier, of Hanover, New Hampshire, to work in his livery stable. He remained there without any interruption from ill health for nearly of quite a year and a half.”
In August 1852 “he engaged with a man who was going to Chile to establish a line of coaches at Valparaiso. He remained in Chile… nearly eight years, occupied in caring for horses, and often driving a coach heavily laden and drawn by six horses.”
His health failed and he left Chile for San Francisco. After “his health improved, and being anxious to work he engaged with a farmer in Santa Clara, but did not remain there long. In February, [1860], while sitting at dinner, he fell in a fit, and soon after had two or three fits in succession. He had no premonition of these attacks, or any subsequent ill feeling.”
Harlow then quotes verbatim, with emphasis, from a letter by Gage’s mother or brother-in-law: “had been ploughing the day before he had the first attack; got better in a few days, and continued to work in various places;” could not do much, changing often, “and always finding something that did not suit him in every place he tried.”

Harlow (1868, 1869): “His mother… informs me that Phineas was accustomed to entertain his little nephews and nieces with the most fabulous recitals of his wonderful feats and hair-breadth escapes, without any foundation except in his fancy. He conceived a great fondness for pets and souvenirs, especially for children, horses and dogs — only exceeded by his attachment for his tamping iron, which was his constant companion during the remainder of his life.”

Phineas Gage viria a falecer em 21/05/1860 após uma série de crises convulsivas, e não se procedeu à autópsia. Somente em 1867, na sua exumação, que seu crânio foi enviado a John M. Harlow.

^ (Tabela)

H.M.

H.M. was likely the most studied individual in the history of neuroscience. Interest in the case can be attributed to a number of factors, including the unusual purity and severity of the memory impairment, its stability, its well-described anatomical basis, and H.M.’s willingness to be studied.

… Because he was the first well-studied patient with amnesia, H.M. became the yardstick against which other patients with memory impairment would be compared.

(SQUIRE, 2009.)

Henry Gustav Molason (1926-2008) — descrito na literatura médica como H.M. — foi um paciente com crises epilépticas com início aos 10 anos de idade e piora progressiva, evoluindo com crises frequentes e não controladas mesmo com uso de altas doses de medicações. A incapacitação decorrente acabou fazendo-o e à sua família concordarem com um tratamento cirúrgico experimental (realizado em setembro de 1953):

An equally radical bilateral medial temporal-lobe resection was carried out in one young man (H.M.) with a long history of major and minor seizures uncontrollable by maximum medication of various forms, and showing diffuse electro-encephalographic abnormality. This frankly experimental operation was considered justifiable because the patient was totally incapacitated by his seizures and these had proven refractory to a medical approach. It was suggested because of the known epileptogenic qualities of the uncus and hippocampal complex and because of the relative absence of post-operative seizures in our temporal-lobe resections as compared with fractional lobotomies in other areas. The operation was carried out with the understanding and approval of the patient and his family, in the hope of lessening his seizures to some extent. At operation the medial surfaces of both temporal lobes were exposed and recordings were taken from both surface and depth electrodes before any tissue was removed; but again no discrete epileptogenic focus was found. Bilateral resection was then carried out, extending posteriorly for a distance of 8 cm. from the temporal tips.

(SCOVILLE e MILNER, 1957.)

A cirurgia possibilitou um melhor controle (apesar de não total) das crises, mas causou uma grave e persistente amnésia. Mais adiante o artigo descreve os achados neuropsicológicos de H.M. e de outros pacientes submetidos a procedimentos cirúrgicos sobre as estruturas mediais do lobo temporal, chegando às seguintes conclusões:

Bilateral medial temporal-lobe resection in man results in a persistent impairment of recent memory whenever the removal is carried far enough posteriorly to damage portions of the anterior hippocampus and hippocampal gyrus. This conclusion is based on formal psychological testing of nine cases (eight psychotic and one epileptic) carried out from one and one-half to four years after operation.

(…)

The memory loss in these cases of medial temporal-lobe excision involved both anterograde and some retrograde amnesia, but left early memories and technical skills intact. There was no deterioration in personality or general intelligence, and no complex perceptual disturbance such as is seen after a more complete bilateral temporal lobectomy.

It is concluded that the anterior hippocampus and hippocampal gyrus, either separately or together, are critically concerned in the retention of current experience. It is not known whether the amygdala plays any part in this mechanism, since the hippocampal complex has not been removed alone, but always together with uncus and amygdala.

Além da descoberta do papel das estruturas mediais do lobo temporal na memória, outras descobertas que se seguiram com o estudo do caso de H.M. foi a descoberta de diferentes modalidades de memória (“declarativa”, “procedural”) — aquelas diretamente dependentes das estruturas mediais do lobo temporal, estas envolvendo núcleos da base, amígdala e cerebelo.

^ (Tabela)

S.M.

O caso de S.M. (1965- ) apresenta uma alteração seletiva da resposta emocional a situações fóbicas ou de perigo decorrente de uma lesão bilateral e isolada das amígdalas pela doença de Urbach–Wiethe.

Um dos muitos testes realizados com S.M. exemplifica a resposta anormal a situações amedrontadoras/ameaçadoras:

…The first fear-inducing situation entailed direct exposure to snakes and spiders, two of the most commonly feared species in the animal kingdom. Interestingly, for many years, S.M. has repeatedly told us that she “hates” snakes and spiders and “tries to avoid them.” To test her real-life behavior, we took her to an exotic pet store and focused on probing for external manifestations of fear with a particular eye toward any signs of avoidance behavior. Upon entering the store, S.M. was spontaneously drawn to the snake terrariums and appeared visually captivated by the large collection of snakes. A store employee asked S.M. whether she would like to hold a snake, and she agreed. S.M. held the snake for over 3 min while displaying a wide range of exploratory behaviors: she rubbed its leathery scales, touched its flicking tongue, and closely watched its movements as it slithered through her hands. Her verbal behavior revealed a comparable degree of fascination and inquisitiveness: she repeatedly commented, “This is so cool!” and asked the store employee numerous questions (e.g., “When they look at you, what do they see?”). During this time period, we asked S.M. to rate her fearfulness on a scale from 0 (no fear at all) to 10 (extreme fear). Her reported experience of fear never surpassed a rating of 2. Moreover, S.M. displayed a compulsive desire to want to “touch” and “poke” the store’s larger and more dangerous snakes, even though the store employee repeatedly told her that these snakes were not safe and could bite. In total, S.M. asked 15 different times whether she could touch one of the larger snakes. She also attempted to touch a tarantula, but had to be stopped because of the high risk of being bitten. When asked why she would want to touch something that she knows is dangerous and that she claims to hate, S.M. replied that she was overcome with “curiosity.” The disconnection between S.M.’s verbally stated aversion to snakes and spiders and her actual real-life behavior was striking. She did not display any signs of avoidance, but instead exhibited an excessive degree of approach (a pattern highly reminiscent of the behavior in monkeys with Kluver-Bucy syndrome). We note that S.M.’s behavior was not merely the result of her feeling comfortable in the relatively safe environment of the pet store, because we later discovered that, in the past, S.M. encountered a large snake outdoors and behaved in a similar manner.

…For S.M., the consequences have been severe. Her behavior, time and time again, leads her back to the very situations she should be avoiding, highlighting the indispensable role that the amygdala plays in promoting survival by compelling the organism away from danger. Indeed, it appears that without the amygdala, the evolutionary value of fear is lost.

(FENSTEIN et al., 2011.)

Mas nada em neurociência é tão simples:

What’s more, pinning a complex emotional state to a single brain structure isn’t straightforward. “When you have to name a structure relevant for fear in the brain, everyone comes up with the amygdala,” Markowitsch [Hans J. Markowitsch, neurocientista na Universidade de Bielefeld] says. “But one could argue that the amygdala cannot act on its own — it’s dependent on connections, on circuits, on other brain regions.”

The study’s authors can’t dismiss other brain regions’ roles in experiencing fear. Yet S.M.’s complete inability to experience the emotion — in a wide variety of forms — highlights the amygdala’s pivotal role in feeling afraid.

(SANDERS, 2010.)

^ (Tabela)

Bibliografia:

Adolphs, R.; Tranel, D.; Damásio, H.; A., Damásio. Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature. 1994;372(6507): 669–72.
Feinstein, Justin S.; Adolphs, Ralph; Damásio, António; Tranel, Daniel. The Human Amygdala and the Induction and Experience of Fear. Current Biology 2011;21:34-8.
Konnikova, Maria. The man who couldn’t speak and how he revolutionized psychology. Scientific American. 08/02/2013. Acessado em junho de 2022.
Macmillan, M. Restoring Phineas Gage: A 150th Retrospective. Journal of the History of the Neurosciences. 2000;9(1):46-66.
Sanders, Laura. Rare Brain Disorder Prevents All Fear. WIRED. 16/12/2010. Acessado em junho de 2022.
Scoville, W.B.; Milner, B. Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery, and Psychiatry. 1957;20(1):11–21.
Squire, L.R. The Legacy of Patient H.M. for Neuroscience. Neuron. 2009 Jan 15;61(1):6–9.
Twomey, Steve. Phineas Gage: Neuroscience’s Most Famous Patient. Smithsonian Magazine. Jan 2010. Acessado em maio de 2022.