Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s & Lozano’s Flashbacks

Abstract

<b><i>Background:</i></b> Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson’s disease, gabapentin for restless legs…). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures. <b><i>Summary:</i></b> James Parkinson’s observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson’s disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced tremor. Both the discoveries of the anterior limbic subthalamic nucleus as a DBS target for OCD and the medial forebrain bundle as a DBS target for depression occurred by chance. Hamani and Lozano observed memory flashbacks in a patient who was undergoing DBS for obesity, which led to the discovery of the fornix as a potential DBS target for Alzheimer’s disease. <b><i>Key Messages:</i></b> In the history of functional neurosurgery, serendipity and observations have resulted in discoveries of several procedures, brain targets for lesioning or DBS as well as new clinical surgical indications. In this era of neuromodulation, this technology should be exquisite in allowing potential serendipitous discoveries, provided that clinicians remain both observant and prepared.

Mapping Lesion-Related Epilepsy to a Human Brain Network

“…Second, it may lend mechanistic insight into why some lesion locations but not others lead to epilepsy. 2 Third, brain lesions can help identify or refine therapeutic targets for brain stimulation, 4 , 5 , 6 and played a role in identifying the thalamus as a therapeutic target for epilepsy. 7 , 8 Given that brain stimulation outcomes in epilepsy remain heterogenous, 9 mapping lesions that cause or do not cause epilepsy may help identify regions or networks that could be targeted for seizure control.…”

Emerging therapies for neuromodulation in Parkinson's disease

“…The introduction of the stereotactic headframe, first in horses and then in humans in the 1960's was a critical advance as stereotactically guided lesions led to more predictable outcomes with less adverse events. One continued challenge in the field was that bilateral lesions led to speech, swallowing, and pseudobulbar side effects [ 14 ]. The neurosurgeon Alim Benabid and the neurologist Pierre Pollack later performed one of the first DBS surgeries contralateral to a previously placed thalamotomy; they observed much fewer speech and swallowing side effects as had been previously observed when using bilateral lesions.…”

A Transatlantic Viewpoint on the Role of Pallidal Stimulation for Parkinson's Disease

“…STN DBS just celebrated its 30th anniversary in Grenoble, France, where it was introduced in the early 1990s 5 . Pallidotomies were the preferred stereotactic intervention for advanced PD before the introduction of DBS 6 . Despite the fact that shortly after the first report of STN DBS was published, 5 a series of patients treated with GPi DBS were reported, 7 STN quickly became the target of choice for PD, and GPi DBS was performed primarily for dystonia 8 .…”

“…5 Pallidotomies were the preferred stereotactic intervention for advanced PD before the introduction of DBS. 6 Despite the fact that shortly after the first report of STN DBS was published, 5 a series of patients treated with GPi DBS were reported, 7 STN quickly became the target of choice for PD, and GPi DBS was performed primarily for dystonia. 8 This was true especially in Europe, where DBS entered the clinical space prior to U.S. Food and Drug Administration approval.…”