“Is There Such a Thing as Too Much Cologne?” A Window Into Frontal Lobe Syndrome

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TALES FROM THE CLINIC

In this installment of Tales From the Clinic: The Art of Psychiatry, we visit the watershed area of executive dysfunction post-brain injury. Frontal lobe syndrome (FLS) can present with a range of perseverative, disinhibited, overactive behaviors that do not meet traditional dementia/neurocognitive disorder criteria; they may resemble mood, anxiety, or psychotic disorders, with atypical features and atypical ages of onset.

Case Vignette

“Mr Yves,” a 64-year-old office manager with a history of hyperlipidemia, hypertension, and stroke, presents at the clinic with his wife, who reports significant behavior and personality changes post-stroke. Notably, she is concerned about his impulsive purchases, necessitating additional storage space. She voices frustration with his impulsive shopping: “it is like he has no brakes, and he has been buying colognes nonstop.” She reports they recently had to rent additional storage space to store all his colognes. They are concerned because a prior urgent care evaluation suggested bipolar disorder, and he had ever had a mental illness history, nor does he have a family history of mood disorders. The symptoms have been quasi-constant since the stroke a year ago, and do not have a cyclical pattern. No psychotic symptoms have been noted.

What is Frontal Lobe Syndrome?

FLS is a relatively rare and complex neuropsychological condition, characterized by a range of cognitive, behavioral, and emotional symptoms resulting from damage to the frontal and prefrontal lobes of the brain. These lobes are crucial for executive functions, including decision-making, inhibition, social behavior, emotional regulation, and voluntary movement. Therefore, damage to the frontal lobes can significantly impact an individual's personality, behavior, and cognitive abilities, leading to profound changes in their quality of life.^1-3

The historical context of FLS can be traced back to the famous case of Phineas Gage in the mid-19th century. Gage was a railroad worker who survived an accident wherein a large iron rod passed through his anterior skull, damaging the frontal lobes. It is reported that after the accident, Gage's personality and behavior underwent dramatic changes; he was more impulsive, disinhibited, and “no longer Gage.” These personal accounts provided the earliest evidence of the frontal lobes' role in personality and social behavior.⁴ This case, among others, laid the groundwork for understanding the critical functions of the frontal lobes and the consequences of their damage.⁵

Management

Clinically, FLS manifests through a variety of symptoms tied together by a common theme of executive dysregulation. These can include dramatic personality changes, poor judgment, inappropriate or risky behavior, lack of impulse control, changes in sexual interest, and emotional outbursts. They can also cause depressive symptoms such as lack of motivation and apathy. FLS can also impact cognition, resulting in difficulties with problem-solving, concentration, planning, and executing tasks.⁶ If the damage is extensive enough to impact other areas of the brain, physical symptoms can also be appreciated. These include hemiparesis, problems with motor movements, and issues with speech or writing.²

The pathophysiology of FLS involves damage to key areas of the frontal lobes, such as the prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Associations between the anatomical location of damage and behavior response have been established. For example, lesions in the ventromedial orbitofrontal cortex can cause impulsive and unrestrained behavior, while lesions in the dorsolateral areas may lead to apathetic states.⁷ Additionally, left-sided lesions are associated with depression-like symptoms, while right-sided lesions are associated with mania.⁸ The causes of frontal lobe disorders can be diverse, including closed head injuries, tumors, neurodegenerative diseases, cerebrovascular disease, and iatrogenic causes. Traumatic brain injury (TBI) is one of the most common causes of frontal lobe damage. Additionally, neurodegenerative diseases such as frontotemporal dementia (FTD), Alzheimer disease, and Parkinson disease can also lead to frontal lobe dysfunction.²

Diagnosing FLS involves a comprehensive evaluation to rule out other organic causes of cognitive impairment (Figure). This includes assessing the patient's medical history for traumatic events, assessing for any history of neurological surgery, conducting physical and neurological examinations, and performing neuropsychological tests to evaluate cognitive function. Imaging studies such as MRI can be used to evaluate for brain atrophy, hematomas, vascular and microvascular pathology, while CT scans may help rule out acute bleeds or hydrocephalus. In cases where FTD is suspected, a deoxyglucose PET scan showing decreased activity in the frontal lobe with sparing of the temporal lobes may be considered.¹

The prognosis for FLS is dependent on etiology. For example, FLS arising from infection, inflammation, and resectable neoplasms may be reversible while damage from trauma, neurodegeneration, and vascular causes carry a much worse prognosis. Management of FLS involves treating underlying causes and providing symptom management to improve the patient's quality of life. Given the complexity and variability within FLS cases, an interprofessional team involving nurses, therapists, physicians, and social workers is needed to provide comprehensive care.¹ The following sections will describe the key treatment options for FLS.

Medical Treatments

For reversible causes of FLS (eg, infection, inflammation, resectable tumors), medical management of these conditions may lead to reversal of FLS symptoms. However, management of irreversible damage is much more complicated. Given the rarity and irreversible nature of most etiologies of FLS, there is a relative lack of literature investigating treatments of the syndrome. Current proposed pharmacological treatments are mainly based on very small studies or case reports and are aimed at symptom management.

Because the frontal lobe is very interconnected, many manifestations of FLS can present with symptoms of neurotransmitter deficits, and effective pharmaceutical treatment varies based on primary symptoms and deficits. For instance, impaired serotonergic signaling in FLS (eg, FTD) can lead to depressive symptoms, which can be treated with SSRIs.⁹ For agitation associated with FLS, atypical antipsychotics can help improve behavioral symptoms and cognition.^10,11 Other potential treatment options for impulse control in frontal lobe syndrome include valproic acid, which has been used to decrease impulsivity in Parkinson disease¹² and TBI,¹³ and lamotrigine, which has been shown to increase frontal lobe network activity in patients with impulsive behavior. Dopamine may be implicated in traumatic causes of FLS. In a randomized controlled trial, administration of bromocriptine following TBI showed increased performance in some tasks involving the prefrontal cortex.¹⁴ Other studies have also shown the effectiveness of dopamine agonists in treating TBI-related aggression and irritability.¹⁵ Amantadine has shown mixed results in limited studies, with 1 observational study showing improved attention in 7 TBI patients, and another 10-person double-blind cross-over study showing no effect in TBI patients.^15,16

Finally, brain stimulation techniques may be useful for treating intractable symptoms of FLS through promoting functional synchronization. Transcranial direct current brain stimulation (tDCS) shows initial promise in the treatment of cognitive and behavioral symptoms, improving neuropsychiatric inventory scores and improving visual reaction times in patients with FTD.¹⁷ Additionally, tDCS may be useful in speech facilitation through frontal cortex stimulation.¹⁸ Studies also indicate that transcranial magnetic stimulation also may be used for treatment of various FLS presentations, such as refractory depression and mood dysregulation.^18,19

Though these treatments provide a foundation for medical management of FLS, further investigations into specific etiologies of FLS may help bolster evidence for current treatments or identify new, experimental treatments for FLS.

Nonmedical Treatments

As many symptoms of FLS may be irreversible, nonmedical treatments are primarily aimed at improving patient quality of life while living with symptoms. For physically debilitating symptoms associated with FLS, occupational and physical therapy can help improve patient autonomy and functioning.¹ Speech therapy may also be useful in FLS presenting with aphasia and apraxia.¹

Treatment of cognitive and behavioral symptoms may also improve patient quality of life. Executive dysfunction, such as impaired planning, foresight, and memory, in FLS may be targeted by cognitive rehabilitation techniques. For instance, patients with stable brain lesions and self-reported executive dysfunction undergoing goal management training (GMT), a technique involving persistent attention towards goals, showed improved attention to response compared to patients who did not undergo GMT.²⁰ While other nonpharmacologic treatments of FLS are lacking in evidence, music therapy may show minor benefit for behavioral symptoms in patients with dementia; direct evidence for its use in FLS is lacking but may serve as an option for patients not responding to other therapies.

Concluding Thoughts

Overall, FLS is a rare and poorly studied condition that can be caused by a variety of etiologies. Symptoms of FLS pertain to impaired executive dysfunction, including but not limited to: dramatic personality changes, poor judgment, inappropriate or risky behavior, lack of impulse control, changes in sexual interest, emotional outbursts, depressive or agitated symptoms, and difficulties with problem-solving, concentration, planning, and executing tasks. Diagnosis of FLS can be challenging given the variable etiologies of the condition and the wide differential but should involve a comprehensive history and physical with relevant imaging, along with additional studies to rule out other potential causes of frontal lobe dysfunction. Some cases of FLS may be reversible with treatment of underlying conditions, but for most cases, FLS causes irreversible damage of the frontal lobe. Treatments are aimed primarily at managing symptoms of FLS and improving patient safety and quality of life. Care must be taken to avoid diagnosing FLS as a primary psychiatric entity as this may link to missed treatment opportunities for underlying conditions.

Mr Balasubramanian is a medical student atTexas A&M University School of Medicine. Ms Pham is a medical student atTexas A&M University School of Medicine. Dr Safavi is an assistant professor of Psychiatry & Behavioral Sciences at Baylor College of Medicine and attending physician at Methodist Hospital, Houston.

References

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