The Curbsiders podcast

#278 Neuro Mystery Case with The CPSolvers

June 7, 2021 | By

Neuro Ddx tips Drs. Reza Manesh and Rabih Geha

Delve into the neuro Ddx with expert diagnosticians the @CPSolvers, Drs. Reza Manesh (@DxRxEdu) and Rabih Geha (@rabihmgeha). Play along as they solve a neurology mystery case, and give us a tour of the neuraxis
No CME for this episode, but claim it for past episodes at!


  • Producer: Matthew Watto MD, FACP
  • Writer (case): Daniel Minter MD (@dminter89)
  • Show Notes: Matthew Watto MD, FACP
  • Cover Art: Sawyer Watto
  • Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
  • Editor: Matthew Watto MD (written materials); Clair Morgan of
  • Guests: Reza Manesh MD and Rabih Geha MD

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Show Segments

  • Intro, disclaimer, guest bio
  • Weakness and Falls
  • Localization on the neuraxis
  • NM junction
  • Lung Mass
  • Cognitive Autopsy
  • Outro

Neuro Mystery Case 

70F with h/o diabetes presents with a fall. She had several months of progressive bilateral lower extremity (LE) weakness, along with proximal muscle weakness of the upper extremities (UE). On exam we detect ptosis, bifacial weakness, and hyporeflexia.

Neurologic Weakness

Weakness Thought Train on CPSolvers site

CPSolvers schema on bilateral LE weakness

Localize the lesion to the brain, spinal cord, cauda equina, peripheral nerve, NM junction, or muscle. Often we assume a single “elegant lesion” that explains all neurologic symptoms. BUT, don’t forget to consider multiple lesions! Neurologist, Dr. Aaron Berkowitz, recommends that we localize the lesion, and then consider the time course to prioritize the differential diagnosis (Ddx).

Upper Motor Neuron (UMN) lesions usually cause hyperreflexia, spasticity, and upgoing toes. But, in the acute setting patients may have hyporeflexia.

Miller-Fisher Variant of Guillain-Barre: Acute onset of ataxia, hyporeflexia and ophthalmoplegia (Check out the NIH-NINDS summary).


Brain lesions often have cognitive symptoms along with bowel or bladder dysfunction. 

Guillain-Barre – usually lacks bowel and bladder symptoms, which can differentiate it from other causes of bilateral weakness. 

Proximal Weakness

Usually due to MYOPATHY. ALS can initially present similar to inclusion body myositis as can a plexopathy (e.g. sometimes seen in diabetes). An elevated CK or statin use can point us to myopathy. Hyporeflexia is usually absent with myopathy unless it is very advanced.

Peripheral Nerve vs NM Junction

Are you seeing a disorder with features of nerve and muscle involvement (e.g. proximal muscle weakness and hyporeflexia)? Consider an NMJ (neuromuscular junction) lesion. 

Further break it down to:

  1. Nerve side (presynaptic e.g. Lambert-Eaton, Tick-paralysis, and Botulism)
  2. Synaptic cleft (e.g. organophosphate toxicity)
  3. Muscle side (postsynaptic e.g. Myasthenia Gravis*).

*Ptosis, plus a spared pupil? Think Myasthenia Gravis. 

Ice pack test (Sethi Neurology 1987): Place ice pack on the patient’s eyelid. This causes increased acetylcholine and the ptosis will improve in Myasthenia Gravis.  

Wt loss

Split this into inflammatory vs non-inflammatory causes.

Inflammatory: Infection, Malignancy, Autoimmune

Non-inflammatory: Muscle weakness, Cognitive dysfunction, Malabsorption, etc.

Lung Mass

1. Infection: Cavitary lesions, Abscess, Tuberculosis, Fungal “omas”

2. Inflammatory: Sarcoidosis, GPA, Rheumatoid Nodules

3. Malignancy: Metastatic lesions, Carcinoid, Small Cell Lung Cancer, Non-small Cell Lung Cancer 

Reza’s NSCLC mnemonic = “A SAD Lung” – adenocarcinoma [peripheral], squamous [central], large cell [peripheral].

Lambert-Eaton Myasthenic Syndrome

A paraneoplastic syndrome of the presynaptic neuromuscular junction caused by an auto-antibody against Voltage gated Calcium channels (VGCC). Small cell lung cancer is a frequent association. Clinical symptoms include proximal muscle weakness, hyporeflexia, and sensory symptoms. Ptosis can also be seen. On EMG there is reduced amplitude of the compound muscle action potentials, and improvement with repetitive stimulation (Kesner Neurol Clin 2018).

Cognitive Autopsy

Reflect on performance to improve your skills for the future. For this case, Rabih points out that a neurologist’s neuro exam is superior and often required to pick up subtleties that might be missed by a less experienced clinician. Reza reminds us that the neuro Ddx is dependent upon localization and the time course of symptoms.


  1. Finding Joy in Medicine by Reza Manesh
  2. One by One by One by Aaron Berkowitz @AaronLBerkowitz 
  3. CPSolvers website and YouTube
  4. Reza’s Twitter @DrRxEdu and YouTube channel
  5. Rabih’s Twitter @rabihmgeha
  6. Virtual Morning Report (International edition) – 

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our links and buy something we earn a (very) small commission, yet you don’t pay any extra.


Listeners will practice their clinical reasoning skills as they pertain to this neurology mystery case.

Learning objectives

After listening to this episode listeners will…  

  1. Develop a framework to localize neurologic lesions on the neuraxis
  2. Recall common causes of neuromuscular junction disorders


Drs. Manesh and Geha report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 


Minter D, Manesh R, Geha R, Williams PN, Watto MF. “#278 Neuro Mystery Case with The CPSolvers”. The Curbsiders Internal Medicine Podcast. Final publishing date June 7, 2021.

CME Partner


The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit and search for this episode to claim credit.

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