Introduction In 1935 Moniz inaugurated a surgical procedure

Introduction

Surgical
interventions for neuropsychiatric disorders are becoming increasingly popular
among clinicians in recent years. The majority of patients diagnosed with a
neuropsychiatric disorder are successfully treated with pharmacological or behavioural
interventions, yet there are a number of individuals who appear to be resistant
to these forms of treatment and consider surgical treatment as an option. This
essay will focus on the role that surgery has on neuropsychiatric disorders,
including a brief history of the origins of modern brain surgery and how it has
developed into what we see today. The efficiency of specific interventions including
transcranial magnetic stimulation, vagus nerve
stimulation, and deep brain stimulation on treating neuropsychiatric disorders,
as well as neuropsychiatric outcomes of surgical treatments will be discussed.

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History of Neurosurgery

The origins of modern neurosurgery for neuropsychiatric disorders was
first developed in the 1930’s when clinicians focused on the correlation
between an individual’s brain and their behaviour. The neurologist associated
with the first surgical treatments for neuropsychiatric disorders was Egas
Moniz. In 1935 Moniz inaugurated a surgical procedure in the treatment of
psychosis. He proposed that interrupting some of the connections between the
prefrontal lobes and other parts of the brain would be beneficial for psychotic
patients. After over 100 procedures it was deemed a success and Moniz noted a
significant improvement in the neuropsychiatric symptoms of psychosis in his
patients (Fukikura, 1993). However, the were sparse records of the follow-up
from surgery, and several patients were sent to institutions and never heard of
again, leading to dissatisfaction in the quality of these studies. Nonetheless
these procedures gave rise to a new treatment of neuropsychiatric disorders and
helped pave the way for other neurologists to develop these procedures further.
Freeman and Watts modified the procedure of severing connections in the white
matter tracts which proved successful in treating the symptoms of
neuropsychiatric disorders, but not without consequences. The adverse effects
of these surgical procedures ranged from postoperative seizure disorders,
infections, and in some cases death (Neumaier et al., 2017).

 

Lobotomy

The development of the transorbital frontal lobotomy proved to be
crucial in the evolution of psychosurgery. It severed connections in the
prefrontal lobe and was performed as treatment for patients with schizophrenia,
manic depression, as well as many other psychiatric disorders (Neumaier et al.,
2017). This procedure was relatively easy to perform which led to its
widespread use, and non-surgeons often carried out the procedure. The procedure
was enthusiastically promoted and received during this time. In the 1930’s in
the US, over 400,000 patients lived in psychiatric institutions, and the cost
of treating mental illness was substantially high (Mashour et al., 2005). Thus,
mental illness proved to be a great burden on society and lobotomies proved to
be a cost-effective way of decreasing the number of psychiatric patients in
hospital and asylums. This surgery also allowed individuals to reintegrate back
into society following surgery. Successful cases of the lobotomy were praised
in many journals, however reports of follow-up neurologic sequelae became more
evident. Scientific literature reported that the efficacy of the lobotomy was
dubious, the clinical indications were poorly defined, and the side effects
including inertia, disinhibition, and decreased attention span, could be severe
(Lapidus et al., 2013). Unqualified practitioners were performing surgeries in
unsterile conditions, increasing the risk of serious and sometimes fatal
sequelae. These observations led to the conclusion that the treatment was worse
than the disorder, and the popularity of lobotomies decreased. In addition to
this, pharmacological treatment of neuropsychiatric disorders was introduced in
the 1950’s. Medications such as chlorpromazine widely replaced the use of
neurosurgical treatments of psychiatric disorders. The cost-effectiveness and
comparable safety of pharmacological treatments was widely recognised by
clinicians which lead to a tentative end to psychosurgery (Lapidus et al.,
2013).

 

Modern Surgical Treatments

Following the development of pharmacological treatments in the 1950’s,
the rate of surgical treatments for neuropsychiatric conditions dramatically
decreased. The majority of patients with neuropsychiatric disorders improved
following pharmacological or therapeutic treatment, such as cognitive
behavioural therapy (CBT), however there were a minority of patients who were
resistant to treatment and were said to have refractory disorders. In the late
20th century many different surgical interventions have been developed with
more targeted approaches, aiming at reducing the incidence of complications and
personality changes. This modern-day psychosurgery is practiced by a
multidisciplinary team and is assessed based on standardised rating scales
(Neumaier et al., 2017). One such method is transcranial magnetic stimulation
(TMS), a surgical treatment to reduce seizures in patients diagnosed with refractory
epilepsy. This noninvasive procedure uses a coil to stimulate small regions of
the brain and has proven to be effective at reducing the number of seizures
(Theodore, 2003). However, the long-term effects are unknown due to lack of
clinical experience. Vagus nerve stimulation (VNS) is growing in popularity in
treating drug-resistant epilepsy. Stimulation of the vagus nerve has shown to
reduce number of seizures over a 2-year period in children with drug-resistant
epilepsy (Orosz et al., 2014). Studies involving adult patients yielded similar
results and the adverse effects were minimal. Thus, VNS is becoming
internationally recognised as one of the most effective treatments for
refractory epilepsy. Although these methods are successful at treating epilepsy,
these procedures do not have a benefit to treating other neuropsychiatric
disorders. The remainder of this essay will focus on Deep Brain Stimulation
(DBS), a surgical procedure that involves delivering targeted electrical
stimulation to specific brain regions, using permanently placed electrodes, for
the alleviation of symptoms (Williams & Okun, 2013). DBS is currently used
in treating a variety of neuropsychiatric disorders, which will be discussed.

 

Parkinson’s Disease

The resurgence of DBS in recent years is largely due to surgical
treatments of movement disorders, with Parkinson’s Disease (PD) being the main
focus. PD is a neurodegenerative condition that affects motor and nonmotor
thalamocortical circuitry within the basal ganglia. Changes in the basal
ganglia are believed to manifest as tremor, rigidity, bradykinesia, apathy, and
sometimes even depression (Williams & Okun, 2013). Drugs such as levodopa
are used to treat PD, and most patients respond well to this treatment in the
first years of the illness. Although, as the disease progresses, a small but
significant number of individuals do not respond well to medical treatment and
continue to display symptoms that have a negative impact on their lives. The
first studies pioneered by Benabid and colleagues used individuals in these
circumstances and discovered that high frequency stimulation of the subthalamic
nucleus resulted in significant improvements in tremor, rigidity, and
bradykinesia, which allowed for pharmacological doses such as levodopa to be
decreased by 60% in patients with advanced Parkinson’s disease (Benabid et
al., 1994). Numerous studies were replicated since Benabid’s work and a
meta-analysis of subthalamic nucleus DBS showed similar outcomes in
improvements in PD symptoms, with quality of life improving 14-24%. These
analyses also determined that DBS was substantially superior to pharmacological
treatment of PD symptoms in advanced PD (Williams & Okun, 2013) Although
these studies reported positive results, the trials were short in duration with
most lasting only 6-12 months. Further longitudinal follow-up trials are
necessary to determine the benefits of DBS and if it should be the preferred
treatment of choice in PD. In addition to this there is a significant incidence
of negative side effects following DBS which include depression, anxiety,
suicide attempts, or psychosis, (Schuepbach, 2013). These adverse effects will
be discussed in more detail at a later point.

 

Tourette Syndrome

Tourette Syndrome (TS) is a neuropsychiatric disorder characterised by
simple and complex motor tics, vocal tics, and frequently obsessive-compulsive
symptoms (Kurlan, 2014). Onset of TS typically occurs before the age of 21 and
goes through a process of increased and decreased severity of symptoms. The
underlying aetiology of TS is unknown although genetics appear to play a part,
control of basal ganglia motor function appears to be disturbed and there is
evidence of dopamine transmission dysfunction in individuals with TS. Typical
treatment usually involves medications that block or lessen dopamine, but some
patients appear to be resistant to pharmacological treatments and see no
improvements. Due the success of DBS in the basal ganglia in PD, clinicians
have tested out if DBS in the basal ganglia leads to improvements in symptoms
of individuals with treatment-resistant cases of TS. One of the first
successful surgical treatments of TS placed stimulation electrodes in various
locations of the basal ganglia and demonstrated that stimulation of the globus
pallidus resulted in improvements in motor and vocal tics (Houeto, 2005). In
one of the largest studies to date on DBS treatment of 48 patients with TS, 60%
reported at least a 50% reduction in symptoms. However, some patients
experienced adverse effects following treatment. 23% required the removal of
the electrodes due to complications and infection, and up to 29% reported no
improvement in symptoms (Servello et al., 2016). It is clear from this evidence
that DBS may be a promising treatment for those with refractory TS, however
there is a clear need for further methodologically rigorous and larger
randomised studies to determine if DBS is the best way forward in treating
symptoms of TS.

 

OCD

TS is typically classified as a movement disorder although it can be
argued that TS is also a neuropsychiatric disorder due to the manifestation of
certain symptoms. Individuals with TS often display obsessive compulsive
symptoms, lack of impulse control, and a variety of other behavioural symptoms
(Muller, 2007). There is also an abundance of evidence that shows a high rate
of comorbidity between TS and other disorders. Depressive symptoms and ADHD
rates in those with TS are between 25-55%. The comorbidity with Obsessive
Compulsive Disorder (OCD) appears to be even higher, having been described in
72% of patients in study consisting of 1374 participants with TS (Hirschtritt,
et al., 2015). This paved the way for further development of DBS in the
treatment of obsessive compulsive disorders. OCD is an anxiety disorder that is
characterised by repeated thoughts or sensations, and engaging in repeated
behaviours in response to these thoughts. Traditional treatments of OCD involve
cognitive behavioural therapy and pharmacological interventions such as
benzodiazepines, but only 70% of patients with OCD respond to these treatments
(Kohl et al., 2016). These results show that DBS is an effective treatment
method, but little is known about the long-term effects of this treatment.
Future studies will need to look at the long-term efficacy of DBS on larger
sample sizes. Another critical step in the advancement of DBS as a treatment of
OCD is to determine the pathophysiology of OCD. A combination of brain imaging
before and after implantation could potentially provide insight into identifying
specific regions associated with OCD, which would allow for enhanced efficacy
(Le Jeune, et al., 2010).

 

Depression

Major depressive disorder is the most common of neuropsychiatric
disorders and is currently the leading cause of disability with a lifetime
prevalence of 20-25% in women and 7-12% in men (Wang et al., 2017). Major
depressive disorder is a mood disorder that severely interferes with everyday
life. It is characterised by persistent low mood, feelings of guilt, anhedonia,
and in some cases, suicidal ideations. Depression can be effectively treated in
the majority of patients by either medication or psychotherapy such as
cognitive behavioural therapy, but up to 20% fail to respond to standard
interventions (Fava, 2003). Functional neuroimaging has played a critical role
in determining the regions in the brain that are affected in those with
depression, with the limbic-cortical pathways and overactivity of Brodmann’s
area 25 (BA25) being associated with the disorder. Advances in surgical
treatment of other disorders involving the limbic system, for example PD, using
DBS has influenced clinicians to look at the effects of DBS on depression.
Mayberg et al., (2005) study looked at reducing BA25 activity using DBS with
the aim of producing clinical benefit on 6 patients with refractory depression.
All patients reported acute effects and lightening of mood, and at a 6-month
follow-up, 4 participants reported noticeable decreases in depressive symptoms.
This study suggested that disrupting activity in the limbic-cortical pathways
using DBS can effectively reverse symptoms in treatment-resistant depression. The
study was limited as it consisted of only 6 participants, future studies would
require more participants to determine the effectiveness of this treatment. Given
the experimental nature of DBS, short-term and long-term effects need to be
examined. One longitudinal study assessed depression severity and adverse
effects of individuals who underwent DBS for depression had follow-up
appointments 1, 3, and 6 years post-surgery. The average positive response rate
between years 1 and 3 were 62-75%, and the last follow-up visit after 6 years
had an average response rate of 64%, with these patients reporting reduced
severity of symptoms and improvements in social functioning (Kennedy et al.,
2011). No significant adverse effects were reported although two participants
died by suicide during a depressive relapse. Current data on DBS suggest that
DBS is an effective treatment for refractory depression but additional trials
with longer duration and larger samples are needed to confirm these findings.

Neuropsychiatric outcomes of DBS (movement
disorders)
Although DBS has proven to be effective at treating refractory
neuropsychiatric disorders, the enthusiasm is overshadowed by reports that some
patients with PD developed neuropsychiatric symptoms following surgery that
impaired quality of life, despite recovering full motor potential (Houeto et
al., 2002). An area of concern are the reports of DBS patients committing
suicide despite positive outcomes. To assess whether DBS is beneficial to use
within a psychiatric setting, a meta-analysis of data obtained over 10 years
was carried out to determine the neuropsychiatric outcomes of DBS treatment of
PD. Most adverse side-effects were procedure related, such as infection. The
most prevalent neuropsychiatric disorder following treatment was depression
which presented in 2-4% of patients. The rate of suicide attempts was 0.3-0.7%
and suicide completion rates were 0.16-0.32% (Appleby, 2007). This analysis
provided evidence that DBS is an effective treatment for movement disorders
with low risk of adverse neuropsychiatric symptoms. The rate of suicide
following DBS is high, therefore patients should be screened both prior to
treatment and monitored post-surgery for suicide risk. Additionally, there is
evidence of anxiety, mania, and new-onset psychosis following DBS for PD in
older patients (Piccoli et al., 2015). Guidelines for patient selection for DBS
include neuropsychological assessment but do not require psychiatric
evaluation. Future studies should aim to have a comprehensive pre-surgical
evaluation and follow-up included with DBS patients to carefully determine the
risk for neuropsychiatric disorders following surgery.

Conclusion

To conclude, surgical treatments display benefits overall for patients
with refractory neuropsychiatric disorders. Lesioning and lobotomies helped
pave the way for modern neurosurgery demonstrating that dysfunctional circuits
in the brain need to be looked at. TMS and VNS are successful non-invasive
treatments for epilepsy, showing few long-term adverse effects. DBS has shown
to reduce symptoms in PD, TS, OCD, and depression, thus improving most
patients’ quality of life. Studies have demonstrated that DBS may have adverse
effects in a small minority of patients, including new-onset neuropsychiatric
symptoms, and suicide risk. To lessen the risk of this, psychiatric
pre-screening and follow-up monitoring should be introduced to decrease the
likelihood of these negative effects. Overall, the benefits of DBS outweigh the
possible disadvantages, but further larger standardised, double blind trials
are needed to establish the long-term effects of this surgical treatments.
Possible future implications could include DBS on other neuropsychiatric
disorders such as schizophrenia, Alzheimer’s disease or other forms of
dementia.