Pharmacologic Treatment of Oscillopsia from Nystagmus -CEW

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======Pharmacologic Treatment of Oscillopsia from Nystagmus======

  * Recommendation depends on the type of nystagmus since drug efficacy differs substantially between nystagmus types. 
  * Evidence base is limited (small crossover RCTs and case series, mostly very low-certainty)
  * Treatment is symptomatic—aimed at reducing slow-phase eye velocity to improve visual acuity and abolish illusory motion
  * No agent reliably abolishes nystagmus, effect sizes are modest, and most data come from very small studies—so treatment is often individualized with trial-and-error 
  * Monitoring for ataxia, fatigue, and dizziness

====Acquired pendular nystagmus (APN)==== 
Often from multiple sclerosis or oculopalatal tremor:

  * **Gabapentin** (typically up to ~2400 mg/day; trial doses 300 mg four times daily)
  * **Memantine** (up to 40–60 mg/day)
    * In a 47-patient placebo-controlled trial gabapetin and memantine were superior to placebo and improved visual acuity, and a double-masked crossover trial found both effective at reducing eye speed and improving acuity, with individual patients responding better to one or the other.[3][2]
    * Gabapentin is generally preferred first-line on tolerability grounds—memantine caused more discontinuations (18.8% vs 6.7%) and can exacerbate MS symptoms, whereas gabapentin was better tolerated.[4][2]
  * **Topiramate** (e.g., 50 mg twice daily) has produced dramatic improvement in refractory APN in a case report when gabapentin/memantine were only partially effective.[5]
  * Anticholinergics (trihexyphenidyl, transdermal scopolamine) are largely ineffective and not recommended; results have been inconsistent.[3][2]

===Gabapentin Guidelines===
  * Titrate up over 1-3 weeks
    * Start low (e.g., 300 mg/day) and increase every few days as tolerated toward 1,200 mg/day divided TID–QID, going higher (up to ~2,400 mg/day) if partial response and well tolerated. 
    * In refractory cases doses as high as 1,800 mg three times daily have been used before adding another agent.
  * Target doses: ranged from 900 mg/day up to 2,400 mg/day
    * Thurtell crossover trial used1,200 mg/day
    * Nerrant trial used **300 mg four times daily (1,200 mg/day)
    * EFNS review cites benefit at doses up to 2,400 mg/day
    * Averbuch-Heller trial used up to 900 mg/day    
  * Renal dosing:
    * gabapentin is renally cleared and requires dose reduction in renal impairment (a critical safety point in older or MS patients with bladder/renal issues).
  * Key adverse effects/monitoring
    * Unsteadiness/ataxia is the main dose-limiting effect—especially in patients with pre-existing cerebellar ataxia
    * Somnolence, dizziness, and peripheral edema. 
    * Monitor gait and sedation at each titration step; 
    * Overall it was the better-tolerated drug, with only ~6.7% discontinuing

===Memantine Guidelines===
  * Titrate up over 1-3 weeks
    * Conventional approach is to start 5 mg/day and increase by 5 mg/week to 20 mg/day
    * Further escalation toward 40 (to 60) mg/day is done gradually and only as tolerated
    * Target doses studied
      * 40 mg/day in most trials (Thurtell, EFNS)
      * 10 mg four times daily (40 mg/day) in Nerrant
      * 40–60 mg/day in the Starck MS study, where 60 mg added benefit in some patients. 
      * Note these exceed the standard Alzheimer maximum of 20 mg/day, so higher doses are off-label and titrated cautiously
  * Renal dosing: reduce dose in severe renal impairment.
  * Key adverse effects/monitoring
    * Lethargy and drowsiness are most common
    * Dizziness, confusion, and headache
    * Discontinuation was higher than gabapentin (~18.8%, including one serious adverse event). 
    * In MS: may worsen MS symptoms and cognition in MS patients gabapentin is preferred first-line, and if memantine is used, select patients without significant cognitive impairment and titrate cautiously

===Common Guidelines===

  * Efficacy endpoints 
    * Near and distance visual acuity
    * Patient-reported oscillopsia
    * Reduction on eye-movement recording/EOG when available. 
    * Trials targeted a ≥50% reduction in nystagmus amplitude/frequency
  * Tolerability
    * Assess gait/ataxia, sedation, and cognition at each dose step; 
    * Renal function guides dosing for both drugs.
  * Approach
    * do an individual trial of one drug, then the other (and sometimes combination or dose reduction to minimize side effects)
    * Effects appear within the ~2-week windows used in trials, so each agent can be assessed over a few weeks

<WRAP round box 60%>
^Parameter^Gabapentin^Memantine^
|Starting dose |300 mg/day|5 mg/day|
|Titration |↑ every few days as tolerated |↑ 5 mg/week|
|Target dose|1,200 mg/day (up to 2,400) divided TID–QID|40 mg/day (up to 60)|
|Main adverse effects|Ataxia/unsteadiness, somnolence, edema |Lethargy/drowsiness, dizziness, confusion|
|Discontinuation rate|~6.7% |~18.8% |
|Renal impairment|Dose reduce |Dose reduce (severe)|
|MS-specific caution|Preferred first-line|May worsen MS symptoms/cognition|
</WRAP>

====Downbeat and upbeat nystagmus====

  * Aminopyridines 
    * 4-aminopyridine (potassium channel blocker)
    * 3,4-diaminopyridine 
    * Reduce slow-phase velocity and oscillopsia (two RCTs support use), with 4-AP possibly more potent; 
    * the main side effect is transient perioral/distal paresthesia.[1][6]

====Jerk nystagmus==== 
  * Memantine- jerk nystagmus responds less well to medication than others

====Periodic alternating nystagmus==== 
  * Baclofen (up to ~30 mg/day)

====Summary by nystagmus type====
<WRAP round box 80%>

^ Nystagmus type               ^ Preferred agent(s)              ^ Typical dosing      ^ Evidence/notes                                        ^
| Acquired pendular (MS, OPT)  | Gabapentin (1st line) | Up to 2400 mg/day   | Superior to placebo, better tolerated                 |
| :::                          | Memantine                       | Up to 40-60 mg/day  | Superior to placebo, Topiramate for refractory cases  |
| Downbeat / upbeat            | Aminopyridines (4-AP, 3,4-DAP)  | 10-20 mg            | Reduce slow phase velocity, paresthesia common        |
| Jerk                         | Memantine                       | up to 40-60 mg/day  | Greater response than gabapentin in crossover trial   |
| Periodic alternating         | Baclofen                        | up to 30 mg/day     | Agent of Choice                                       |

</WRAP>


====References====

  - [[https://pubmed.ncbi.nlm.nih.gov/29505103/|Interventions for Eye Movement Disorders Due to Acquired Brain Injury. Rowe FJ, Hanna K, Evans JR, et al. The Cochrane Database of Systematic Reviews. 2018;3:CD011290]]
  - [[https://pubmed.ncbi.nlm.nih.gov/20437565/|Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Thurtell MJ, Joshi AC, Leone AC, et al. Annals of Neurology. 2010;67(5):676-80]]
  - [[https://pubmed.ncbi.nlm.nih.gov/21906211/|Nystagmus and oscillopsia. Straube A, Bronstein A, Straumann D, European Federation of Neurologic Societies. European Journal of Neurology. 2012;19(1):6-14]]
  - [[https://pubmed.ncbi.nlm.nih.gov/31169568/|Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes. Nerrant E, Abouaf L, Pollet-Villard F, et al. Journal of Neuro-Ophthalmology. 2020;40(2):198-206]]
  - [[https://pubmed.ncbi.nlm.nih.gov/36220602/|Teaching Video NeuroImage: Dramatic Response to Topiramate in Acquired Pendular Nystagmus From Multiple Sclerosis. Murphy OC, Calabresi PA, Gold DR. Neurology. 2023;100(1):47-48]]
  - [[https://pubmed.ncbi.nlm.nih.gov/25903394/|Pharmacotherapy of Vestibular and Cerebellar Disorders and Downbeat Nystagmus: Translational and Back-Translational Research. Strupp M, Zwergal A, Feil K, Bremova T, Brandt T. Annals of the New York Academy of Sciences. 2015;1343:27-36]]
  - [[https://pubmed.ncbi.nlm.nih.gov/24057832/|Pharmacotherapy of Vestibular Disorders and Nystagmus. Strupp M, Kremmyda O, Brandt T. Seminars in Neurology. 2013;33(3):286-96]]
  - [[https://www.ovid.com/journals/jner/abstract/10.1007/s00415-009-5309-x~acquired-pendular-nystagmus-in-multiple-sclerosis-an?redirectionsource=fulltextview|Acquired Pendular Nystagmus in Multiple Sclerosis: An Examiner-Blind Cross-Over Treatment Study of Memantine and Gabapentin. Starck M, Albrecht H, Pöllmann W, Dieterich M, Straube A. Journal of Neurology. 2010;257(3):322 7]]
  - [[https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.410410620|A Double-Blind Controlled Study of Gabapentin and Baclofen as Treatment for Acquired Nystagmus. Averbuch-Heller L, Tusa RJ, Fuhry L, et al. Annals of Neurology. 1997;41(6):818-25]]
  - [[https://pubmed.ncbi.nlm.nih.gov/21087742/|Pharmacological Management of Symptoms in Multiple Sclerosis: Current Approaches and Future Directions. Thompson AJ, Toosy AT, Ciccarelli O. The Lancet. Neurology. 2010;9(12):1182-1199]]


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