Labyrinth of brain scans leading to a DNA helix, symbolizing the diagnostic journey of neurological disorders.

Is It MSA-C or SPG7? How to Spot the Difference in Late-Onset Cerebellar Ataxia

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Nico Varela in Health & Wellness December 2025 • 4 min read.

"Unraveling the complexities of ILOCAs: A deep dive into differentiating between Multiple System Atrophy of cerebellar type (MSA-C) and SPG7 mutations for accurate diagnosis and care."


The realm of neurological disorders presents numerous diagnostic puzzles, with idiopathic late-onset cerebellar ataxia (ILOCA) standing out as a particularly intricate one. First described by Harding, ILOCA refers to the gradual onset of cerebellar ataxia (CA) without a clear cause, typically emerging around age 50 and sometimes accompanied by other neurological features. The quest to pinpoint specific etiologies has revealed that ILOCA is not a single entity but likely encompasses various sporadic and genetic conditions.

As genetic understanding has expanded, certain conditions have been identified within the ILOCA umbrella, such as Friedreich's ataxia, spinocerebellar ataxias (SCAs), Fragile X premutation, Gordon Holmes syndrome, and SYNE1 mutations. However, a significant portion of late-onset CA cases remains idiopathic, with multiple system atrophy of cerebellar type (MSA-C) often considered the most frequent underlying cause.

This article sheds light on a specific case of a patient initially diagnosed with ILOCA, who was later found to have a mutation in the SPG7 gene, known for causing hereditary spastic paraplegia. This case report, combined with a review of existing literature, underscores the importance of considering SPG7 mutations as a potential cause of the MSA-C phenotype within ILOCA, emphasizing the need for accurate differentiation to guide appropriate management and treatment strategies.

Decoding the Symptoms: MSA-C vs. SPG7

Labyrinth of brain scans leading to a DNA helix, symbolizing the diagnostic journey of neurological disorders.

To illustrate the diagnostic challenges, consider the case of a 68-year-old woman who developed progressive walking difficulties in her early fifties. She described her condition as feeling "drunk," experienced frequent backward falls, and felt stiff after standing for more than 15 minutes. Additionally, she reported dizziness upon sudden sitting or standing, as well as urinary urgency with occasional incontinence. Her medical history included hypertension and migraine, but there was no family history of neurological diseases.

During examination, she exhibited hypomimia, gaze-evoked nystagmus (involuntary eye movements) when looking to the left, slow saccades (rapid eye movements) on the vertical plane, and mild upgaze restriction. Motor function tests revealed a right upper limb intention tremor, bilateral dysmetria (lack of coordination), and dysdiadochokinesia (inability to perform rapid alternating movements). She also had slight lower limbs spasticity, symmetrical brisk deep tendon reflexes, a broad-based gait, and impaired postural reflexes.

Key Differences to Consider:
  • Brain Imaging: Brain MRI, conducted more than 10 years after the onset of symptoms, excluded cerebellar, pons, and basal ganglia abnormalities, except for some ill-defined signal changes potentially related to small vessel disease. Her DATscan, a test to assess dopamine transporter function, was normal.
  • Initial Diagnosis: Based on the clinical presentation, a movement disorder expert diagnosed her with MSA-C. However, further investigations, including metabolic and autonomic studies, came back normal or negative.
  • Genetic Testing: Subsequent next-generation sequencing (NGS) revealed a homozygous missense variant [c.1529C>T, p.(Ala510Val)] in exon 11 of the SPG7 gene.
This case highlights the overlapping features between MSA-C and SPG7-related conditions. The patient's symptoms, including urinary dysfunction, spasticity, and hyperreflexia, initially pointed towards MSA-C. However, the genetic testing ultimately revealed the underlying SPG7 mutation, demonstrating the importance of considering genetic testing in atypical presentations of ILOCA.

The Takeaway: Why Accurate Diagnosis Matters

In conclusion, this case underscores the diagnostic challenges in differentiating between ILOCA, MSA-C, and SPG7-related conditions. While clinical features may initially suggest MSA-C, genetic testing is crucial for accurate diagnosis, especially in atypical cases. By recognizing SPG7 mutations as potential mimics of MSA-C, clinicians can ensure appropriate management and treatment strategies, ultimately improving patient outcomes and quality of life.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is Idiopathic Late-Onset Cerebellar Ataxia (ILOCA), and why is it important?

Idiopathic late-onset cerebellar ataxia (ILOCA) refers to the gradual appearance of cerebellar ataxia without an identifiable cause, usually beginning around age 50. It can sometimes include other neurological symptoms. The significance lies in understanding that ILOCA is not a single disorder but can be caused by various conditions, including genetic mutations like SPG7 and sporadic conditions like MSA-C. The implications of this are the necessity to determine the specific cause to provide effective management and treatment, improving a patient's quality of life.

2

What is Multiple System Atrophy of cerebellar type (MSA-C) and how does it relate to the broader context?

Multiple System Atrophy of cerebellar type (MSA-C) is often considered as the most frequent underlying cause of ILOCA. MSA-C is a neurodegenerative disorder. Differentiating between MSA-C and SPG7-related conditions is crucial, as they present overlapping symptoms. The diagnostic process involves evaluating symptoms, brain imaging, and genetic testing. The implications of an accurate MSA-C diagnosis are that targeted treatments can be initiated early.

3

What is the significance of SPG7 mutations in the context of ILOCA?

SPG7 mutations cause hereditary spastic paraplegia. In the context of ILOCA, SPG7 mutations can present symptoms that mimic MSA-C, making diagnosis challenging. This case demonstrates the need for genetic testing when clinical symptoms aren't conclusive. The implications are the correct identification of the underlying genetic cause is essential for accurate diagnosis, management, and treatment strategies for patients with ILOCA-like symptoms.

4

What are the key differences between MSA-C and SPG7 that clinicians should consider?

The key differences between MSA-C and SPG7-related conditions include brain imaging findings and genetic test results. For example, a DATscan assesses dopamine transporter function and can help differentiate. Genetic testing such as next-generation sequencing (NGS) is key for identifying SPG7 mutations, as it can reveal the underlying cause of the symptoms when the clinical presentation is not definitive. Implications of recognizing these differences are that they directly influence treatment strategies and the overall approach to managing the condition.

5

Why is an accurate diagnosis crucial when differentiating between ILOCA, MSA-C, and SPG7?

Accurate diagnosis is paramount because it guides management and treatment strategies. In cases where the initial diagnosis is MSA-C, but the underlying cause is an SPG7 mutation, the treatment approach would differ. Precise diagnosis influences the patient's care, including symptom management, and potential therapeutic interventions. Accurate diagnosis ensures patients receive the most appropriate and effective care, improving outcomes and the quality of life.

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