Understanding General Paralysis of the Insane: Causes, Symptoms & Treatment

What is General paresis of the insane?

Alternative Names:General paresis of the insane, General paralysis of the insane (GPI), Paralytic dementia, Syphilitic paresis, Neurosyphilis.

General paresis, also known as general paralysis of the insane (GPI), paralytic dementia, or syphilitic paresis or neurosyphilis, is a severe neuropsychiatric disorder affecting the brain and central nervous system. It results from late-stage syphilis and is caused by chronic meningoencephalitis and cerebral atrophy due to untreated infection by the syphilis spirochete Treponema pallidum.
Historically, GPI was a major cause of admission to asylums during the 19th century. It is characterized by progressive mental deterioration, paralysis, and eventual death, making it one of the most devastating diseases in the history of psychiatry. The condition primarily affects the frontal and temporal lobar cortex, leading to cognitive decline and motor impairment.
The disease affects approximately 7% of individuals infected with syphilis and is more common in regions with limited access to treatment, particularly in developing countries. It is also more prevalent among men. GPI differs from mere paresis, which can have multiple other causes and usually does not affect cognitive function.

Causes of General paresis

General paralysis of the insane (GPI), is caused by Treponema pallidum,the bacterium responsible for syphilis. It occurs as a late-stage manifestation of neurosyphilis, typically in individuals who have had untreated or inadequately treated syphilis for many years.
The infection spreads throughout the body, eventually invading the central nervous system (CNS). This leads to chronic inflammation of the brain and spinal cord, causing progressive degeneration of brain tissue. As a result, affected individuals experience cognitive decline, motor dysfunction, and neuropsychiatric symptoms.
General paresis usually develops 10 to 30 years after the initial syphilis infection. Due to advancements in antibiotics, neurosyphilis and consequently, general paresis is now very rare.

Pathophysiology of General paresis

General paresis develops due to the persistent presence of Treponema pallidumand the host's immune response (a complex interplay). The immune system's efforts to eliminate the bacterium trigger chronic inflammation, gliosis, and neuronal degeneration. Over time, these pathological changes lead to widespread cerebral atrophy, with significant damage to the frontal and temporal lobes.

Signs & Symptoms of General paresis

Symptoms of GPI can be categorized into neurological, psychiatric and cognitive manifestations. The onset typically occurs after 10 – 30 years of initial syphilis infection. Symptoms begin from subtle neurological to progressive severe dementia.

The condition affects motor and sensory functions, leading to:

• General muscle weakness
• Seizures – Epileptic seizures in some cases.
• Gait disturbances
• Tremors – Fine tremors, particularly in the hands, which may worsen over time.
• Pupillary Abnormalities – Argyll Robertson pupils, which constrict during accommodation, but do not react to light (a hallmark sign).
• Dysarthria – slurred, speech difficulty.
• Loss of bladder and bowel control in a more severe stage

Patients may experience significant mental health disturbances, including:

• Personality Changes – Apathy, increased irritability, euphoria, inappropriate behavior, and mood swings.
• Psychosis – Hallucinations, delusions (grandiose, paranoid, nihilistic), and melancholic, sometimes mimicking schizophrenia.
• Depression – Persistent sadness, hopelessness, and loss of interest in activities (anhedonia).

Cognitive decline is a defining feature of general paresis, characterized by:

• Mutism
• Confusion and disorientations
• Memory Loss – Progressive deterioration of both short-term and long-term memory.
• Executive Dysfunction – Impaired planning, decision-making, and problem-solving abilities.
• Dementia – In advanced stages, severe dementia can significantly impact daily functioning.

Diagnostic Test & Investigations

The diagnosis of general paresis requires a comprehensive approach, incorporating clinical evaluation, serological testing, and neuroimaging.

A thorough medical history is essential, particularly any past history of syphilis. Physicians assess psychiatric, neurological, and cognitive symptoms to identify characteristic manifestations of the disease.

Neuroimaging can reveal characteristic brain abnormalities associated with general paresis and serological test can confirm to clinical diagnosis

• Cerebral Atrophy– Diffuse atrophy, particularly in the frontal and temporal lobes.
• White Matter Lesions– Hyperintensities indicating gliosis and chronic inflammation.
• Nontreponemal Tests– Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) for initial screening.
• Treponemal Tests– Fluorescent Treponemal Antibody Absorption (FTA-ABS) and Treponema pallidum particle agglutination (TP-PA) for specific confirmation.

• Head CT Scan & MRI
• Nerve Conduction Tests
• Spinal Tap (Lumbar Puncture)

Treatment of General paresis

The primary goals of treatment are to eradicate the infection, slow disease progression, and prevent further neurological damage. While treatment can stop new damage, it cannot reverse existing nerve damage, making early intervention crucial.

Penicillin remains the gold standard for treating neurosyphilis and general paresis. The recommended regimen includes: Aqueous Crystalline Penicillin G– Administered intravenously at doasge 18-24 million units 4 hourly a day for 10-14 days. For penicillin-allergic patients, ceftriaxone or doxycycline may be considered under specialist guidance.

Since antibiotic therapy cannot reverse existing neurological damage, symptomatic treatment is essential:

• Psychiatric Medications:Antipsychotics, antidepressants, and mood stabilizers help manage psychiatric symptoms.
• Antiepileptic:Drugs Used to control seizures.
• Cognitive Rehabilitation:Programs aimed at improving cognitive function and daily living skills.

A multidisciplinary approach is vital for long-term management:

• Neurologists:Monitor neurological symptoms and treatment response.
• Psychiatrists:Address psychiatric symptoms and provide psychotherapy.
• Social Workers:Assist with social support and resources for patients and families.

Nursing Management of General paresis

These measures are crucial for the optimal care of individuals affected by General paresis

• Reassure patient and relative
• Monitor and record vital signs
• Provide emotional support for relatives
• Assess cognitive functions
• Monitor signs of psychosis
• Ensure safe environment by removing potential hazards
• Assist patient with ADL
• Educate caregivers on patient condition, safe and effective patient care
• Monitor patient for suicidal ideations
• Encourage physical therapy
• Collaborate with a neurologist and psychiatrist for medical management
• Administer prescribed antipsychotics
• Monitor drug side effects