Introduction

Overview of Gerstmann Syndrome

Definition and historical background

Gerstmann Syndrome (GS) is a rare neurological disorder that, in most cases, is caused by either a brain injury or a developmental disorder. In very rare instances, children with very high IQ may also suffer from it. It is a non-hereditary condition.¹ It was first named in 1924 when neuroscientist Josef Gerstmann described a rare neurological disorder in some patients.²

Key symptoms

The main symptoms are 4, although in some cases there may be additional cognitive defects:¹ 

• Agraphia
• Acalculia
• Finger agnosia, and
• Left-right disorientation

Importance of Study

Relevance in understanding neurodegenerative diseases

Once neurodegenerative diseases develop, they are permanent conditions that last a lifetime. This is why researchers aim to use rational approaches based on a deep understanding and knowledge of these diseases. It is an ongoing effort to develop effective therapeutic treatments that can either cure these diseases or at least slow their progression as much as possible.^3,4

Overview of how neurodegenerative diseases impact cognitive and motor functions

These diseases damage parts of your brain and nervous system, causing the cells in the central nervous system to stop functioning or die. As the disease progresses, the loss of abilities in the affected areas, which previously controlled certain functions, becomes more pronounced.^3,5

Clinical Features of Gerstmann Syndrome

Core Symptoms

Detailed description of the four main symptoms

Dysgraphia prevents or hinders a person from translating their thoughts into written language, despite having received education and being of an age and mental capacity suitable for it. In essence, it is a specific learning disorder related to written language.⁶

Acalculia is characterised by the loss of the ability to process numbers and perform calculations. When acquired, such as in Gerstmann syndrome, it can lead to severe social limitations due to the importance of numbers in daily life.⁷

Finger agnosia is often considered a variant of autopagnosia, but it affects only the fingers. People with finger agnosia have difficulty naming fingers, moving fingers upon request, and pointing to a specific finger.^2,8

Left-right disorientation impairs the ability to distinguish left from right, whether for oneself or others.^2,9

Neuroanatomical correlation: Parietal lobe involvement, particularly the angular gyrus

Lesions caused by Gerstmann syndrome are specific and primarily affect the posterior parietal lobe in the dominant hemisphere, usually the left hemisphere, though in some cases it can be the right hemisphere. Notably, the angular gyrus and adjacent structures in the parietal lobe are particularly affected. Recent studies have shown that lesions causing this disorder do not necessarily have to be in the parietal lobe; they can also occur in the middle frontal lobe of the dominant hemisphere.²

Associated Cognitive Impairments

Additional cognitive deficits

This syndrome can also produce additional symptoms such as:²

• Apraxia 
• Optic Ataxia 
• Cognitive impairment
• Numbness or weakness

Neurodegenerative Diseases Associated with Gerstmann Syndrome

Alzheimer’s Disease

Prevalence and presentation of Gerstmann Syndrome in Alzheimer’s patients

Alzheimer's disease also often presents with the four classic cognitive functions affected by Gerstmann syndrome. A study investigated whether these four symptoms occur due to a shared neural network or simply due to the anatomical proximity of independent neural networks. It was found that in Alzheimer's disease, the symptoms do not cluster together and lack correlation, unlike in Gerstmann syndrome. This suggests that the symptoms may be related due to the anatomical proximity of different neural networks responsible for these functions, explaining their simultaneous appearance.¹⁰ 

Frontotemporal Dementia (FTD)

Frontotemporal dementia results from damage to the nerve cells in the frontal and temporal lobes of the brain.¹¹

Among the subtypes of FTD that could be related to Gerstmann syndrome is posterior cortical atrophy (PCA). PCA involves degeneration of the occipitoparietal region and presents with the same four characteristics of Gerstmann syndrome.¹²

Other Neurodegenerative Disorders

Parkinson’s Disease: Rare but possible occurrence

There is a theory suggesting that Gerstmann syndrome, a disconnection syndrome, shares some similarities in its pathogenesis with Parkinson’s disease. This is inferred because both conditions have been found to result from disconnections in certain brain pathways.¹³

Pathophysiology

Role of the Parietal Lobe

Angular gyrus and its connections to other brain regions

The angular gyrus is located in the anterior parietal lobe and has a horseshoe shape. It is situated between the parietal, occipital, and temporal lobes, playing a crucial role in coordinating, managing, and connecting these different functional areas.¹⁴

Disruption in neural networks leading to Gerstmann Syndrome

As previously mentioned, Gerstmann syndrome is a disconnection syndrome, but only a few studies have directly investigated the disconnection patterns related to it. A recent case study revealed interesting data about how the disconnection pattern of Gerstmann syndrome may function. It found that the subcortical tracts connecting the angular gyrus (AG), the supramarginal gyrus (SMG), the intraparietal sulcus (IPS), and the postcentral gyrus (PCG) were fully affected in the damaged left hemisphere. The left superior longitudinal fasciculus (SFL) was also affected, unlike the right one.¹⁵

Neurodegenerative Mechanisms

Accumulation of pathological proteins (e.g., tau, amyloid-beta) in the parietal lobe

Beta-amyloid accumulates in the brain, forming plaques that disrupt cellular function.¹⁶

Tau is a protein that normally stabilises microtubules. However, if altered, it can detach from the microtubules and adhere to other cells, forming threads that develop into tangles within neurons.¹⁶

When Amyloid-β and tau proteins accumulate and spread through the brain's neural networks, they affect key areas for neuronal communication, such as the parietal lobe.¹⁷

Neuroinflammation and its contribution to symptom development

In some cases, when the immune system fails to eliminate the inflammatory stimulus, chronic inflammation may occur, leading to the release of neurotoxic factors and worsening of the disease. Traumatic brain injuries causing Gerstmann syndrome induce a widespread neuroinflammatory response, which, if not repaired, can lead to chronic inflammation and ongoing damage to adjacent areas.¹⁸

Neuroimaging and Neuropathology

MRI, CT scans, and PET findings in patients with Gerstmann Syndrome

MRI (Magnetic Resonance Imaging) uses strong magnetic fields and radio waves to create highly detailed images of the body, including the brain. It involves lying in a large tube with high-power magnets.¹⁹

CT (Computed Tomography) also provides detailed images of the body, but it uses a series of X-rays taken rapidly in a circle around the patient.^20,21

PET (Positron Emission Tomography) is a type of imaging that uses radioactive materials to show the function of organs and tissues.²²

Diagnosis and Differentiation

Diagnostic Criteria

Criteria used to diagnose Gerstmann Syndrome in clinical settings

The criterion usually focuses on the presence or absence of the four characteristic symptoms of the disease. It is also crucial to verify that these symptoms are not attributable to other conditions. In children, this condition is often detected at school. Children will generally have difficulties with spelling, basic arithmetic calculations, and distinguishing between left and right.²³ Neuropsychological tests are essential because they allow for the measurement of brain function.²⁴

Differential Diagnosis

Distinguishing Gerstmann Syndrome from other parietal lobe syndromes

The main differential diagnosis will be with posterior cortical atrophy. These two syndromes cause agraphia in the patient. To differentiate it from GS, it is essential to know other symptoms such as hemineglect, optic ataxia, and verbal alexia.²

Conditions with overlapping symptoms

• Alzheimer's Disease
• Disconnection Syndrome
• Developmental Disorders

Treatment and Management

Symptomatic Treatment

Occupational therapy

Occupational therapy aims to improve your ability to perform everyday tasks if you're experiencing difficulties. Occupational and speech therapies may help reduce dysgraphia and apraxia.^25,26

Psychological support

Psychological support refers to a variety of interventions and therapeutic strategies aimed at alleviating stress, frustration, and emotional challenges. These types of therapies can greatly assist in managing emotions more effectively.²⁷

Technological assistance

Current technology has advanced significantly, and devices like calculators and word processors can assist children with this disorder in an academic setting.²⁸

Cognitive rehabilitation strategies

Cognitive stimulation involves the patient's participation in a variety of activities and discussions, often in group settings. All of these activities aim to improve overall cognitive and social functioning.^29,30

Disease-Specific Therapies

Treatment approaches in the context of underlying neurodegenerative diseases

Currently, many treatment protocols are required in the field of neurodegenerative diseases, although none have yet been able to halt the progression of the disease. Therefore, one of the current approaches focuses on a better understanding of the precise mechanisms that initiate neurodegenerative diseases in order to discover new treatment alternatives.³¹

Potential benefits of early intervention

It has been found that children with early symptoms of the disease can experience some improvement through intensive speech training.²

Multidisciplinary Care

Role of neurologists, psychiatrists, occupational therapists, and caregivers

Neurologists are doctors with the necessary training to diagnose conditions, conduct tests like CT scans, and even perform certain procedures.³²

Neuropsychiatrists are responsible for conducting neurological research, psychometric studies, and other additional investigations that can be applied in the diagnosis, treatment, and rehabilitation of patients.³³

Occupational therapists aim to help patients manage their daily tasks and activities, promoting their physical, social, and emotional well-being.³⁴

Caregivers, in their primary role, provide care and support to the patient by ensuring they have a balanced diet, exercise regularly, and follow their medication regimen.³⁵

Research and Future Directions

Current Research

Ongoing studies on the relationship between Gerstmann Syndrome and neurodegenerative diseases

Some studies have shown that various lesions can also affect the left middle frontal lobe. Links have been recorded with the development of Gerstmann Syndrome in cases of:¹³

• Progressive multifocal leukoencephalopathy
• Multiple sclerosis
• Cortical atrophy

Advances in neuroimaging and biomarkers

Biomarkers in neuroimaging currently use brain imaging techniques to visualise the brain's morphology (MRI), function, microenvironment, metabolism (e.g., PET), or molecular content and lesions.³⁶

Future Research Directions

Potential for early detection of neurodegenerative diseases through Gerstmann Syndrome

The potential for early detection of neurodegenerative diseases through Gerstmann Syndrome lies in observing its four main symptoms. All these symptoms are linked to cortical degeneration of a part of the parietal lobe, which can also be affected in the early stages of various neurodegenerative diseases, such as posterior cortical atrophy (PCA).¹²

Exploring new treatment avenues

There are many medications currently in development for rare neurological diseases based on genetics. Most of these include antisense technology, gene therapy, and genetic editing technologies. One of the most promising technologies today is antisense oligonucleotides (ASOs).³⁷

Summary

Gerstmann Syndrome is a rare neurological disorder characterised by four symptoms: finger agnosia, left-right disorientation, agraphia, and acalculia. It can result from brain lesions or developmental disorders and arises from damage to the parietal lobe, specifically the angular gyrus.

The symptoms of the syndrome are linked to neural disruptions caused by protein accumulations and inflammation. Diagnostic imaging techniques such as MRI, CT, and PET are used to diagnose it. Treatment focuses on managing symptoms through cognitive therapy and rehabilitation. Efforts are ongoing to improve early diagnosis and develop new treatments.

Understanding Gerstmann Syndrome is crucial because its symptoms and their relationship with other conditions also provide insights into neurodegenerative diseases, aiding in better diagnosis and therapy development.